NOTE: This spoiler was submitted by Jeremy.
The film is preceded by a trailer for "Machete Kills Again...In Space!", which features the titular hero on an intergalactic mission, starring Danny Trejo, Michelle Rodriguez, Alexa Vega, Lady Gaga, Justin Bieber as a robot named Bleep (which Machete destroys), and Leonardo DiCaprio as "The Man in the Silver Mask" (with the sub-note that the actor is subject to change).
The actual film starts off with a team of military men arriving at the Arizona-Mexico border, where they start unloading crates filled with high-tech weaponry. They're cornered by Machete Cortez (Danny Trejo) and Sartana Rivera (Jessica Alba), both of whom are aware that these men are planning on selling weapons to the cartel. Sure enough, the cartel arrive right on cue. They whip out their guns and kill all the military men. Machete and Sartana fight back, with Machete slaughtering them with his, well, machete. The cartel leader prepares to kill Machete, stating that "if a man kills a legend, he becomes a legend himself." That's when three helicopters show up with masked men hopping out and shooting the cartel. Sartana pleads with Machete to help her fight these other men, and she goes around to the back of the military truck to find a large missile in the back. A man in a luchador mask walks up to her and shoots Sartana in the head, killing her. Machete finds her body and falls on his knees in despair, just as he is apprehended by the masked men.
Machete is set to be hanged in the office of Sheriff Doakes (William Sadler) after being accused of murdering Sartana. Doakes tells his deputy Clebourne (Samuel Davis) to kick the stool from beneath Machete's feet, which he does, but Machete doesn't die. Instead, he stares viciously at the two men. The phone rings, and Clebourne answers, then passes it to Doakes, saying it's the President. Doakes answers and then grabs his gun to shoot the noose to free Machete. He takes the phone and growls, "This is Machete."
Machete is escorted to the White House to meet President Rathcock (Charlie She--er, I mean, Carlos Estevez), who informs Machete that a Mexican cartel member-turned-revolutionary named Marcos Mendez (Demian Bichir) has a plan to launch a powerful missile at Washington unless Mexico is invaded to put an end to the corruption. Ratchcock orders Machete to find Mendez and kill him. Machete refuses the mission until Rathcock grants him U.S. citizenship and tells him to do this for his country and for Sartana.
Arriving in San Antonio, Texas, Machete meets his handler, Blanca Vasquez, aka Miss San Antonio (Amber Heard). She shows off her arsenal of guns and blades, including a three-bladed machete that catches Machete's eye. She briefs him on Mendez's plan and tells him to go to Acapulco to find a young woman named Cereza (Vanessa Hudgens), as she will lead Machete to Mendez. Miss S.A. then has sex with Machete.
Miss S.A. flies Machete to Acapulco where he parachutes down to find a brothel run by Madame Desdemona (Sofia Vergara). She orders her band of prostitutes to make sure they get their earned money from any customer who comes in, then sends them away as Machete comes in. He takes out a picture of Cereza and requests to see her. Desdemona leaves to get her, only to come back with a gun. She fires at Machete, prompting him to run and get shot at by the other prostitutes. He runs into a room to find Cereza, who willingly goes with him. He grabs her and jumps out the window.
Machete and Cereza wait at a dock for their ride to see Mendez. She reveals that she is Desdemona's daughter and that Mendez was once a normal man who became insane, earning him the nickname "Mendez the Madman". The two are picked up on a speedboat with a man named Zaror (Marko Zaror) and two revolutionaries. They all board a helicopter to head to Mendez's lair. While they're flying, Zaror says "Mendez sends a message," and he shoots Cereza in the stomach and throws her out of the helicopter.
The helicopter arrives at Mendez's lair. True to his reputation, he is a maniacal man who has a very large missile standing in the middle of the room, and the trigger is wired to his heart, so if he dies, the missile launches. He says there are only two people who know how to disarm it. Zaror kills the only doctor in the room, which leaves only one other person who knows, and he is all the way back in the U.S. To make matters worse, Mendez pulls the trigger on his chest, which leaves 24 hours before the missile launches. Thinking quickly, Machete grabs Mendez and takes on his henchmen, using his triple-bladed Machete to slice into Zaror's stomach and make his way out while killing other goons. He knocks Mendez unconscious and runs to the helicopter. Zaror runs out to fight Machete, but he sticks his hand in Zaror's stomach to pull out his intestine and throw it into the helicopter's blades, pulling Zaror up and slicing him to pieces. Machete boards the helicopter with Mendez, then receives a call from Miss S.A. He tells her that he is taking Mendez across the border, leading her to call Rathcock. Machete informs them both about the missile's trigger being wired to Mendez's heart, so he is going to find the man who sold him the missile, coming from a company called Voz Tech.
As the helicopter flies over the ocean, two revolutionaries on a speedboat try to shoot at Machete. He jumps out with Mendez and lands in the boat. He knocks out one revolutionary while fighting the other, then grabbing a grappling hook, shooting it at the helicopter, and sticking it to the man, which pulls him up, shreds him, and causes the helicopter to explode. Machete then steers the boat to the docks, but there are more revolutionaries waiting for them. He sticks the gas in the speedboat on full speed and jumps out with Mendez, right before the boat flips over, crashes into the dock, and kills the men with the boat's turbines.
Machete pulls Mendez to land, where Mendez suddenly drops his madman persona and begins to speak to him calmly. He appears to have no recollection of the trigger on his heart and is distraught when Machete tells him that he ordered Cereza to be killed.
At a Mexican radio station, a goon enters and orders the host to read off an announcement over the radio - a hit has been issued on Machete and Mendez, offering over $20 million to whoever kills them. This is heard by Machete's ally Luz (Michelle Rodriguez), as well as Doakes and Clebourne.
Elsewhere in Mexico, a man (Walton Goggins) enters a bar. He asks for a martini but the bartender tells him they only serve tequila and chango. The man orders the chango and then reveals to the bartender that he is the notorious killer known as El Camaleon, for nobody has ever seen his face. He kills the bartender and the other two men in the bar, then leaves. He pulls off his mask to reveal a new disguise (Cuba Gooding, Jr.). He receives a notice about the hit on Machete, and then kills a tourist couple and takes their car.
Machete and Mendez go to a Mexican restaurant where everybody recognizes them and watches them with the intent to kill. A cop named Chepo (Julio Oscar Mechoso) aims his gun at Mendez's head, calling him "loco" ("crazy" in Spanish). This causes Mendez to revert to his madman persona and he begins to punch Chepo's face in, with Machete finally shooting him in the chest. The police arrive to arrest the two, forcing Machete to grab Mendez, kill the restaurant's workers, and cut the gas line to destroy the restaurant.
Desdemona is in her brothel whipping a man tied to a table while telling him why she hates men - her father used to sexually abuse her as a child until she chewed his balls off. She wraps the whip around the man's neck and breaks it. One of the prostitutes, KillJoy (Alexa Vega) comes in to tell Desdemona about the hit on Machete. She then hands Desdemona a machine gun bra to prepare herself.
El Camaleon arrives at a garage and learns that Machete was spotted in Villa Guerrera. He asks the man at the garage for directions, but when he fails to answer him properly, he kills the man. He then notices the camera which has captured his face. He shoots it and removes his mask to become a woman (Lady Gaga).
Machete takes Mendez to a clinic after he was shot in the neck at the restaurant. While he's being treated, a prostitute spots them and informs Desdemona and her girls. Machete spots them and puts blood bags in the microwave, causing them explode and spray on the prostitutes. Desdemona opens fire with her machine gun bra, but Machete manages to outrun her. He grabs a defibrillator and uses it on the bra to throw Desdemona several feet away. He once again grabs Mendez and runs.
The duo make it to a shop to get a car. There is a man in a wheelchair there who is willing to turn them in as a group of assassins arrive on the scene. Machete shoots the man's oxygen tank, which pushes the wheelchair into plain sight of the assassins, and they open fire on him and launch a rocket at the man. Machete and Mendez get into an armored vehicle and flee. As they continue to make their way to the border, Mendez tells Machete who he used to be - he was never part of the cartel, but rather, he was Mexico's first secret agent who planned to end the corruption in the country, but his supervisor betrayed him and had his wife and daughter beaten and murdered before his eyes. He went crazy and killed the supervisor and his men, leading him to join forces with the man who sold him the missile.
With about 13 hours before the missile launches, Machete and Mendez arrive close to the border. However, Desdemona and her prostitutes are following, and El Camaleon is not far behind. Machete throws a blade into Desdemona's vehicle that is set to blow up, forcing her and her girls to jump from the vehicle. With it being stranded, it causes El Camaleon to hit the car and overturn his (or her) car. Desdemona runs out with a crotch gun to fire at Machete, but he outdrives her. Defeated, she and her girls walk away.
The wall of the border is too big for Machete to drive through, so Mendez informs him of a wall with graffiti to drive through. It opens to a tunnel and that allows them to burst underground into the U.S. Waiting for them on the other side is Doakes and Clebourne. Doakes aims his gun to kill the two but Mendez throws a blade of his own to cut off Doakes's hand. He then breaks his neck before shooting Clebourne in the head. Not long after, a group of masked men similar to the ones from before arrive. Among them is Zaror himself. He decapitates Mendez while the other masked men pump Machete full of lead.
There's a brief campaign ad to re-elect Rathcock for another term, stating his accomplishments with gun laws and legalizing marijuana in 28 states. He then adds "Winning was only the beginning."
Machete wakes up in a pool at Voz Tech Industries. Next to him is Mendez's headless corpse. Standing over Machete is Luther Voz (Mel Gibson), president of Voz Tech and the same man who gave Mendez the missile. Voz holds a jar containing Mendez's still-beating heart while the missile's launch countdown is still going. He tells Machete he is lying in a healing pool, and then takes him on a tour of the place in his "Star Wars"-inspired vehicle. Voz explains that he has seen the future where the world has come to an end, so he has built a rocket that will take him and anybody willing to join him up into space. Additionally, he has been manufacturing genetically engineered super soliders, and unleashes a number of Zaror clones to fight Machete. Machete grabs any weapon that's close to him and he kills all the clones. Voz is impressed before discussing the final part of his plan - including Mendez, he has manipulated people in other countries, including North Korea and Russia, into obtaining missiles to launch all around the world. Machete runs out of there with one of Voz's weapons and hops in the "Star Wars" car. He is followed by Voz's men all the way to an electric fence. The weapon he grabbed is a molecule disabler, which he fires at the goons, causing them to disintegrate. A helicopter arrives, and Machete uses a hook to latch onto the blades to swing around and decapitate the remaining henchmen. He gets into the helicopter which is being flown by Luz.
Luz takes Machete back to her hideout with her group, the Network, and tells him that many Mexican laborers have been abducted mysteriously. He tells her about the missile, and she says she knows someone who can disarm it, but he's not gonna like who it is. It's Osiris (Tom Savini), the hitman from the previous film who killed Machete's friend Padre (Cheech Marin). Osiris asks for a chance to redeem himself, remorseful for killing Padre. Machete is then contacted by Miss S.A. who asks him to meet her at a rendezvous point after she's done with her swimsuit competition. Luz knows that Machete had sex with Miss S.A. and says his judgment is clouded.
Machete meets Miss S.A. at the rendezvous point with Luz, Osiris, and another guy named Tito following closeby. Miss S.A. betrays Machete by saying she offered to bring him back to Voz in exchange for winning the competition to crown her Miss Texas. A gunfight ensues between Voz's goons and Machete's friends. Tito is killed and Machete hops onto the villains' car until one of them shoots him off the roof.
Machete wakes up in the desert and walks until a truck driver (Antonio Banderas) stops to pick him up. His Spanish is noticeably awkward and inconsistent, so he gives up and reveals that he is El Camaleon. In his female disguise, he was able to hail the truck's previous driver before assuming another disguise. He takes Machete out of the truck and makes him dig his own grave, but Machete digs up a tunnel where several Mexicans are sneaking past the border. Machete hops in while El Camaleon has his back turned, and he follows soon after he realizes Machete's gone. Unfortunately for him, he runs into a group of border-patrolling rednecks who shoot him to death. Meanwhile, Machete makes it out. He is picked up by Luz's allies and taken back to her hideout. She addresses all of them on Voz's plan to launch his missile and rounds everybody up to help her and Machete fight back.
Just barely half an hour is left before the missile launches. Machete, Luz, and the Network infiltrate a party thrown at Voz Tech Industries by disguising themselves as the help. Voz is set to bring all the guests with him into space, complete with their own weird futuristic wardrobe. Machete comes in and tells the crowd that Voz plans to bring the world to an end, prompting the Network and Voz's henchmen to engage in another gunfight. Machete runs after Voz while Miss S.A. shoots out Luz's other eye and kills other Network members.
Machete and Osiris find the heart, which Osiris finds too complicated to disarm. Voz enters and shoots the heart, leaving only five minutes left before the launch. He aims his molecule disabler at Machete, but Osiris jumps in and takes the shot to finally redeem himself. Machete and Voz engage in a duel with their own bladed weapons. Voz gains the upper hand and nearly kills Machete, until Machete uses his hook to pull a flamethrower to spit fire in Voz's face, leaving him horribly disfigured. He stumbles into another room to grab the silver mask seen at the beginning in the fake trailer. At the same time, Luz, now blind, fights Miss S.A. She throws her crown at Luz, but she catches it and throws it back at Miss S.A.'s chest, hitting her heart. Luz finishes her off with a blast to the head.
As Machete runs to turn off the missile, Voz succeeds in rounding up the party guests and the Network to bring them with him and the other abducted laborers into his rocket. He also has Luz frozen in carbonite (just as she flips him off). The missile launches with Machete riding it. He cuts the blue wire inside, and the missile falls into a river just as Voz's rocket launches into space. Rathcock and his men find Machete, and he thanks him for saving the world. He asks where Voz is, and Machete points to the sky. Rathcock says he has a new mission for Machete to go into space to get Voz, and before he says anymore, Machete immediately accepts the mission.
Machete goes to the Space X station in an astronaut suit and boards the rocket that will take him up to find Voz and defeat him once and for all, setting the stage for "Machete Kills Again...In Space!" It's also shown that Desdemona and her girls will face off with Machete yet again, leading to a cliffhanger where the masked Voz holds a blade at Luz's neck in front of Machete, swinging the blade before cutting to Rathcock saying he approves this message.
After the credits:
There's an outtake with Michelle Rodriguez "pussy-punching" Amber Heard, which Heard laughs about, followed by Rathcock in space, firing his own badass space guns.