The film opens with newspaper clippings about missing people and a summary of how they were found. Police officials raided the Firefly house and found body parts in the refrigerator, as well as furniture made out of human limbs. They also found enough evidence and corpses in the basement to put the Firefly body count at 75 people. The family would forever be known by the media as "The Devil's Rejects".......
We see Tiny (Matthew McGrory) dragging a naked and mutilated female body through the woods. He is on his way to the Firefly house when he spots numerous police vehicles making their way down to the house as well. Tiny lifts up his burlap sack that is covering his burnt face and looks at the swarm of police as they drive closer and closer to the house. Tiny remains unseen in the forest. The police arrive at the Firefly house and park in front of the house. Their leader is Sheriff Wydell (William Forsythe), brother of Lieutenant George Wydell (Tom Towles) who was killed by the Firefly family in the first movie, "House of 1000 Corpses". The police strap on bullet proof vests and prepare their guns. An officer asks Sheriff Wydell if he thinks they are going to die today. Wydell tells him "dying ain't an option". He pumps his shotgun and gets ready to talk through a speaker box. Inside the house, Otis (Bill Moseley) is sleeping next to a naked female corpse, Baby (Sheri Moon) is fast asleep naked in her room, and Mother Firefly (Leslie Easterbrook) is asleep as well in her bedroom. They are all awakened when Wydell orders them to come out peacefully as they are surrounded by police. Otis looks through a window and sees all the cops. He puts on a shirt and jeans, picks up his pistol, and walks downstairs. Baby puts on some clothes, gets her gun, and goes downstairs along with Mother Firefly. Rufus Jr. (Tyler Mane) is already at the bottom of the stairs in full metal body armor and tells them that they are completely surrounded. Otis says "tell me something I already don't fucking know!". They all wonder where Tiny is, but Mother Firefly says that he left last night and hasn't been back since. Otis and Rufus take positions near the front of the house while Mother Firefly and Baby take positions in the back near the kitchen. Mother Firefly is crying, and says that she remembers that Baby looked like an angel when she was born. Baby and Mother Firefly exchange "I love you" and put on metal masks. Otis puts on his metal mask (his has a skull painted on it) and gets ready to fire.
Wydell and the cops begin to pump the Firefly household full of bullets. The family members inside take cover and then return fire. Otis and Rufus fire machine guns while Baby and Mother Firefly fire pistols. They kill a couple of cops, but are fired upon heavily again by the law enforcement outside. During this shootout, Otis shoots Wydell in the chest but his bullet proof vest catches it. This enrages Wydell even further and he walks slowly towards the house pumping shells from his shotgun. Eventually, he orders for the officers to cease fire and throw in tear gas. Wydell kicks in the door to the gas-filled house and is followed by the other officers (all of whom are wearing gas masks). Suddenly, Otis and the family come out of their hiding places and blast away the cops. The cops around Wydell get hit but he doesn't. Otis, Baby, and Mother Firefly make their way to the kitchen entrance while the police unload their guns into Rufus' body armor. Rufus eventually dies from all the bullets. Mother Firefly sees that her son is dead and goes to his side while Baby and Otis go through a secret tunnel in the house. Wydell orders Mother Firefly to drop her gun, but she points it to her own head and says "you'll never get me". She pulls the trigger, but the gun is out of bullets. Wydell tells her "it looks like it's not going to be that easy".
The main titles and opening credits appear as we see Otis and Baby running through the secret tunnel while their kidnapped victims scream at them. The tunnel leads to a sewer, and Otis and Baby escape using this. They run through a nearby field with their weapons in hand as the police discover the house and all their victims. The police take Mother Firefly away in handcuffs to the police station. A nurse driving by sees Baby lying in the middle of the road. She gets out to see if she is alright. While she does this, Baby holds the woman down as Otis pops out and stabs the woman to death with his knife through her back. They steal her car and drive off. The police, upon further searching through the house, come across several notebooks and pictures of all the people the family has killed. They notice that Captain Spaulding (Sid Haig) is in a lot of the pictures with various dead people, smiling while showing off his bloody hands. Wydell recognizes Spaulding and orders his men to find him.
Meanwhile, we see the Captain having wild, rough sex with a prostitute. After they are done, Spaulding calls her a whore. She then draws a gun on him and says that she is not a whore. Spaulding says "I call them as I see them". She cocks the gun and gets ready to blow his brains out. He says that he's just joking around with her (after all, he is a clown). She laughs and then blows his brains out. Spaulding wakes up (it was all a dream) and we see the woman he is sleeping with is an unattractive husky woman. She asks him if he had a bad dream. Spaulding looks at the rhino he just had sex with and says "it was 50/50". They get out of bed and watch Spaulding's new commercial, showing his new monkey attraction. The commercial is cut short by an important broadcast by the news and Spaulding gets pissed. He gets even more pissed and worried when the news shows the raided Firefly house. They have been dubbed "The Devil's Rejects" by the media. Spaulding gets his gun and jacket when he is called by Baby. It is revealed that Spaulding is Baby's father. She tells him what happened and they agree to meet up at the motel that they said they would meet in case of an emergency. Baby gets back into the car with Otis and they drive away. Spaulding leaves his house and drives off to meet them.
Back at the station, Wydell and several officers interrogate Mother Firefly about the whereabouts of the other family members. She refuses to rat out her own family and says that the cops really just want to have sex with her (she used to be a prostitute). Wydell shows her some notebooks and pictures of her victims, but she is unmoved. Mother Firefly then gets some pictures from a notebook and says that she never knew exactly where to put them. She shows Wydell and it turns out to be his dead brother. She pieces together that this Wydell is related to the one she blew the brains out of and insults them both. Wydell loses it and back-hands her face. He grabs her throat and says "I'm going to kill your whole fucking family!". The other officers pull Wydell from her and they all leave. As they do, Mother Firefly loses it as well and spouts out some craziness, while saying that her family will kill Wydell.
We are brought to Charlie's Frontier Fun Town, which is the place to go for prostitutes. It is run by Charlie Altamont (Ken Foree). His assistant Clevon (Michael Berryman) cleans the place mostly. As Charlie is counting the money he's made, he is surprised by how little cash he's got. Candy (Elizabeth Daily) says that the only customer she got was one farmer who just wanted a hand job. She figures that he is saving his energy to have sex with his sheep. Charlie says that they need to think of new ways to bring in customers. Candy says that she has an idea: she could do a Star Wars theme and dress up like Princess Leia. She figures that a lot of geeks will want to have sex with Princess Leia, and Clevon says he definitely would. Charlie says that he will keep on brainstorming. The phone rings, and Spaulding is on the other line (he's at a payphone). It turns out that they are related, and are brothers. Spaulding gives him the rundown of the situation, and tells him that he's coming to his place to hide from the cops. Charlie doesn't want him coming there, but Spaulding hangs up the phone.
Otis and Baby get to the motel that was agreed upon, but they don't see Spaulding. Otis calls him a "dumb old bitch" and him and Baby exchange insults to each other. He orders her to get a room for them to chill out in until Spaulding gets there. Baby looks around while we come across a traveling band called "Banjo & Sullivan". Adam Banjo (Lew Temple), his wife Wendy Banjo (Kate Norby), Roy Sullivan (Geoffrey Lewis), and their roadie Jimmy (Brian Posehn) are all making fun of Roy's wife Gloria (Priscilla Barnes) because her breasts popped out while she was riding a mechanical bull the night before. The Banjo's and Gloria get settled in room 2, while Roy and Jimmy go out to get ice. On the way to the ice machine, Jimmy says that he thinks he can be a good clown and do his act with bulls. Roy thinks that Jimmy can do something better than that, and sends him to the gas station nearby to get some beef jerky. Roy goes alone to fill up a bucket of ice when Baby runs into him. She is pretending to try to find a cat. Baby flirts with Roy and he obviously likes it. Baby asks to go to his room so that they "can have some fun". Roy says that he can't, as his wife is in his room. Baby then tells him to take her to his room or else her brother (Otis) will kill him. Otis appears with his gun in hand and they all proceed to walk to room 2.
Wendy is in the bathroom taking a shower while Gloria is watching a talk show about satanic stuff. She tells Adam to change the channel as it bores her and is not true at all. Adam does and hears some knocking at the door. He opens it and is shoved onto the bed by Otis. Baby shoves Roy inside onto the bed as well. Otis hears the shower is on and bursts into the bathroom. He drags the still very naked Wendy out of the bathroom and pushes her onto the bed. Adam covers her up with a blanket and a flannel shirt. After exchanging insults with Baby, Otis then asks if there is anyone else with them. Roy says no, but just then Jimmy comes back from the gas station and knocks on the door. Otis orders everyone to be cool and not to make a peep. Baby answers the door and lets Jimmy in. She shoves him onto the floor and Otis shoots him in the forehead, killing him. Everyone screams, and Adam vomits over Wendy and the bed. Otis gets really pissed off at Roy, because this shows that he can't trust him.
Back to Spaulding, his red truck breaks down and runs out of gas. He pulls his car over to the side of the road and wonders what to do next. He sees a woman and her young boy coming out of a building nearby. He approaches them and tells them that he needs to take their car "on account of top secret clown business". He laughs with the woman, and she then asks what he wants. Spaulding asks back "did I stutter, bitch?". The woman orders her son to get into the car and to lock the door (he does). She walks around to the driver's side and tries to open the door, but Spaulding punches her in the face and gets in. The boy is clearly scared, and Spaulding asks him why he doesn't like clowns. The boy won't answer him. Spaulding then tells him that he's going to come back, and if the boy doesn't have a good answer as to why he doesn't like clowns, he's going to kill his entire family. He orders the boy out of the car, and the boy tearfully does. Spaulding drives off to meet his kids (Otis and Baby).
Back at the motel, Baby dances in front of Roy. Otis asks him if he likes what he sees, but Roy says no. Otis asks him if he is queer or something, because he's got a hot piece of ass dancing in front of him and he's not at all excited. Roy says that he is a married man. Otis orders Gloria to get up and to take off all her clothes, since he wants to see what Roy is attracted to. Gloria takes off her pants and shirt, leaving her in her bra and underwear. Otis gets up and runs his gun up and down her body. He eventually gets to the point where he puts his gun down the frontside of Gloria's underwear and forces her to suck his penis. After he's through, he calls her disgusting and shoves her back onto the bed. He then orders Adam and Roy to take a road trip with him. They leave in the "Banjo & Sullivan" van while Baby stays in the room with Gloria and Wendy.
Otis gets Adam to drive them somewhere in the desert. Once they reach their destination (which looks like a junkyard), Otis orders Roy and Adam out of the van. They have to walk the rest of the way. Adam wants to know exactly where he is taking them, and Otis honestly tells them that they are going to dig up some weapons that was buried some time ago and then Otis is going to kill them. Roy and Adam stop walking and plead with Otis for their lives. Otis asks Adam if Wendy gets off whenever he vomits on her. Adam lunges at Otis, but he shoves him aside and aims his gun at Roy's head. Adam then grabs a piece of wood and hits Otis in the head with it. He hits him with the wood a couple of more times, but Otis won't go down that easy. This action, however, caused Otis to lose grip of his gun and Roy tries to retrieve it. Otis jumps on top of Roy and struggles with him. Adam jumps on top of Otis and hits him a couple of times. Otis then takes out his very sharp, very long knife and rams it into Adam's leg. Otis continues to struggle with Roy over the gun. Adam rips the knife out of his leg and is going to use it on Otis. Otis forces Roy to pull the trigger on the gun, and he makes Roy shoot Adam in the neck. Adam goes down. Otis snatches the gun away and proceeds to pistol whip Roy. After he's done, he picks up the piece of wood that Adam used on him and hits Roy in the crotch with it. Otis walks over to the bleeding-to-death Adam, of whom begs Otis to stop. Otis, however, says "I haven't even begun". He shows him what happens to heroes: Otis grabs the piece of wood and bashes Roy's brains out of his head. He then walks over to Adam and tells him that he has something else planned for him. We see Otis begin to slash up Adam's face.
Back at the motel, Baby is watching a singer on TV. Gloria is humming to the song that is playing, and Baby tells her to shut up. Wendy has to pee, and wants to go to the bathroom. Baby says that she could care less about where Wendy pees. If Wendy is to go to the bathroom, Baby wants something in return: she wants Wendy to hit Gloria. Wendy is hesitant, but Gloria assures her that it is okay. Wendy lightly slaps Gloria, but Baby is not happy. She wants her to hit harder. Wendy slaps Gloria harder, but Baby is still not happy. Wendy slaps Gloria the hardest she can. Baby orders Wendy to kiss her and say "Baby, I'm having a great time". Wendy kisses Baby and repeats the line. Wendy goes to the bathroom, but Baby tells her to make it quick. Once in the bathroom, Wendy frantically looks for a way out. She smashes the window with the toilet lid and screams for help. Baby gets up and gets ready to kill her when Gloria grabs Baby's gun and points it at her. Baby asks her why would ! she do that, and we see that Baby is hiding a big knife behind her back. Gloria says that she will pull the trigger. She then yells out to Wendy that everything is fine, and that she can come out of the bathroom. Baby throws her knife into Gloria's chest. Gloria drops to her knees and pulls out the long knife from her chest. Baby pulls down her pants and playfully tells her to "shoot her bottom off". Gloria, near death, raises the gun at Baby's butt and pulls the trigger. Nothing happens. Baby then laughs and says that the gun isn't loaded. Wendy comes out of the bathroom and sees Gloria dying. She pushes her way past Baby and runs outside. Gloria dies.
Wendy is slamming on each door at the motel, screaming for help, but no one will answer her. She runs her way past the pool area and runs into a man who she thinks will help her. The man turns out to be Spaulding. Baby catches up to Wendy and tells her father that she almost got away. By the time Wendy realizes who her "savior" is, he head-butts her and knocks her out. They drag her back to the motel room and tie her up to the bed post (they also gag her). Spaulding asks where Otis is, but Baby says that he is just getting the guns from their secret stash. He says that Otis better not mess it up. Just then Otis bursts into the room and scares the two. He cut off Adam's face and is wearing it as a mask. Otis and Spaulding insult each other, but are called off by Baby. They are all wondering about what to do with Wendy. Spaulding suggests just leaving her for the maid, but Otis says that he has something better in mind. The scene ends with Otis kissing Wendy with Adam's face.
The maid comes around to room 2 and sees that no one is around. She sees that everything is a mess. She opens the bathroom and finds the butchered remains of Jimmy and Gloria in the bathtub. "The Devil's Rejects" and "fuck you" are written all over the wall with blood. As she screams, Wendy comes awake. She was tied to the back of the main door, and Otis has strapped Adam's face onto hers. Wendy breaks free and falls on top of the maid. The maid freaks out and runs away. Wendy wildly chases after the maid, hoping that she will help. When she can't catch up to her, Wendy runs into the middle of the road and tries to wave down a car. Since she's wearing her husband's face, no one will slow down for her. A big truck runs over Wendy and she becomes roadkill. She dies.
Sheriff Wydell and the police are called onto the scene. Wendy's body parts and brains are splattered all over the road. It is a gory mess. Wydell orders a deputy to clean her brains off of the pavement. Wydell then goes over to the maid and shows her pictures of Spaulding, Otis, and Baby. He asks her if she has seen any of them, but she says no. Wydell is called away because he has some visitors: a pair of bounty hunters who call themselves "the Unholy Two". These two men are Rondo (Danny Trejo) and Billy Ray Snapper (Diamond Dallas Page). Wydell orders them to find Spaulding, Otis, and Baby.
Upon further searching of the records from the house, it is discovered that all of the Firefly family member's names are comprised of characters that Groucho Marx has played in the Marx Brothers films. Wydell and the police look into the various character names that Groucho used. They call in a "film expert" to help them, but he turns out to be useless. Wydell then gets a call from the Unholy Two and they tell him that they found out that one of Groucho's character names is used as an alias by Charlie Altamont. They reckon that is where the trio of killers will go next.
We see Otis driving the other two in a stolen car. Spaulding tells him to drive to Charlie's. Otis doesn't trust Charlie, but Spaulding orders him to go there anyway. Baby sees a road sign for ice cream, and she wants Otis to stop for it. Otis says that he won't, because those 20 seconds that they spend there could wind up dangerous to his health. Spaulding and Baby then annoy Otis by repeating that they want "rutti fucking tutti". Otis tells them "there is no ice cream in your future". The next scene shows Spaulding and Baby eating ice cream, and Otis irritated that he actually caved in. Baby offers Otis some of her ice cream, but he refuses. She gets some on his beard, and they all laugh about it while listening to music.
Next, we see Wydell going to the Firefly house by himself and going through the basement. He thinks that he hears Spaulding's voice and sees the top of his head, but when he sees who it really is Wydell freaks out: it is his dead brother George. Wydell asks him what he's doing down there, and George tells him that it is his home now. He doesn't have a choice in the matter, and he is stuck there until the Firefly's die. George urges Wydell to walk "over the line" and kill all of them for him. Wydell suddenly wakes up. It was all a dream. Later that night, he goes to visit Mother Firefly. He sends the guard home, leaving just himself and her. She says that he couldn't resist having sex with her. Wydell winds up stabbing Mother Firefly twice in the chest. She is dead. He pulls the knife out of her chest, leaves it on the table, and walks away.
Otis, Baby, and Spaulding arrive at Charlie's Frontier Fun Town. Charlie walks outside with a shotgun and orders them to put their hands in the air. They do, and Otis is pissed that they came all the way out there just to get held at gun-point. Charlie shoots Spaulding in the face, and the gun is revealed to be a squirt gun. They hug each other and catch up on old times. Otis, Spaulding, Charlie, Baby, and some prostitutes party with each other and get drunk (with the occasional weed). At the same time, Wydell has gone completely berserk and is talking to himself in the mirror. He vows to kill all of them for his brother.
The next morning, Charlie and Clevon leave to go get some chickens. Charlie says that Spaulding makes the best fried chicken. They drive along a road and get to a guy who is selling chickens. The guy asks them if they have sex with chickens. Charlie and Clevon are a bit offended by this. The guy just asks because it looks like they are holding up some sexual tension inside (especially Clevon). Charlie and Clevon especially get weirded out when the guy says that when you cut off the head of a chicken and stick your penis inside, it feels like a vagina. Charlie buys a couple of chickens (for eating) and leaves with Clevon. They don't get far, however, for Wydell blocks the road with his truck. Charlie gets out of his car and walks over to Wydell's truck. Wydell uses the truck door to hurt Charlie's fingers and orders him to keep Spaulding and the two others pre-occupied at his place until midnight. If he refuses, Charlie will be killed. Wydell leaves, and Charlie is left with quite a dilemma.
Wydell goes to the trailer-home of Billy Ray Snapper and meets up with him and Rondo. He tells them that the three will be at Charlie's place at midnight. He doesn't want them to mess this up. Wydell also mentions that he doesn't care what condition they are in, but he wants them alive enough to feel the pain of their victims. The Unholy Two mention how sick and twisted Wydell really is, but he just tells them not to mess up.
That night, Charlie and Spaulding snort some cocaine. Charlie leaves to go to the bathroom. He takes his coke with him ("you're my brother, and I love you...but I love my coke more"). Spaulding then puffs away on a joint. Otis is fooling around with Candy, and Baby is taking a sponge bath while talking to a prostitute. The prostitute leaves to get a cold beer from the fridge. While she does, Rondo sneaks behind her, covers her mouth, and slits her throat. Billy Ray Snapper scratches the record that is playing music. Otis realizes that they have been caught. Rondo orders Baby to get up at gunpoint, and Baby (completely naked) goes to get clothes. Candy grabs Otis' gun and tries to shoot Billy, but he blasts her in the forehead with his gun and laughs. Otis lunges at him, but is promptly thrown out of the window. Wydell comes to where Spaulding is, takes a shot of alcohol, and surprises the clown. Spaulding insults him and his brother, so Wydell shoots Spaulding in the belly. They all find out that Charlie betrayed them. Otis, Spaulding, and Baby are put in the back of Wydell's police truck and they drive back to the Firefly home.
The three killers are tied to chairs in the basement and listen to Wydell talk about how his family has always been demon slayers. Wydell kicks Otis in the crotch and orders him to stay awake. He picks up a picture of a missing girl, then shows Otis a picture of the girl's corpse when she was found in the house. Otis says that she is still worthy of sex. Wydell staples the pictures to Otis' chest. Wydell walks over to Baby and staples some pictures of a girl she killed. Spaulding insults Wydell, so he beats Spaulding almost to death with a pipe. Wydell punches Otis and Baby, and continues to torture them. Throughout this, Wydell gets more and more drunk. He then nails the hands of Otis into the arm-rests on his chair. Wydell unties Baby and tells her to run. He splashes gasoline all over the floor and lights it on fire, leaving Otis and Spaulding to burn to death.
Baby runs outside and through the place where the family kept cows. Wydell grabs an axe and says that Baby is like a rabbit, and that she should run. He chases her up and down the farm. She hides in a barn and runs into Charlie. She's pissed at him for giving them up, but Charlie says that he is going to get them out of there. She says that Otis and Spaulding are still in the house, which is on fire at this point. Charlie puts Baby in a car and says that he will get the others. Before he can, though, Wydell shows up and plunges the axe into Charlie's throat. He rips out the axe and hits him again to kill him. Charlie's dead. Wydell chases Baby out of the car and eventually gets her onto the ground. He begins to choke her to death using his bare hands. A figure appears behind Wydell and lifts him into the air. It is Tiny. Tiny wraps his arms around Wydell, and breaks his neck. Wydell is dead. Baby tells Tiny to save the others from the burning house. Tiny goes inside and to the basement. He rips out the nails out of Otis' hands and frees both him and Spaulding. They all get out alright.
Otis is in the front seat of a car, with his father and sister in the back. He asks Tiny "are you sure you want to do this?". Tiny nods. Otis says that they will come back for him. As Otis and the remaining family members drive away, we see Tiny slowly walking into the house (which is still on fire). We understand that Tiny is going to kill himself. The house blows up with Tiny inside. Tiny's dead.
Otis and his family are driving through the desert, and all three of them think about the good times that they spent together. He suddenly stops the car. A look of disappointment, fear, and sorrow comes across his face. We see just further ahead on that road is a police blockade. He tearfully wakes up Spaulding and Baby in the back seat. They see that they are not going to get away. He gives Baby a gun, and she stands up in the back seat. Otis gives Spaulding the shotgun, and he leans out the right-side of the car. Otis has a gun in his left hand and proceeds to drive with his right. They all fire at the cops while speeding towards them, but there are too many police officers. Otis, Baby, and Spaulding are shot to death by the cops.
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