NOTE: This spoiler was sent in by Michael Z who says... "This spoiler may seem a bit wonky as the movie has no plot to speak of. I know you are looking for spoilers only and not movie reviews, so I will try my best not to editorialize. The description of the movie pretty much speaks for itself."
It is the year 10,001 BC. A caveman is running from something. A mammoth almost steps on him and misses. The caveman lands face down in a pile of mammoth dung. He runs into Wolf from American Gladiators and gets hit in the nards a couple of times. For some reason, Wolf starts telling him that he wanted to register "Bam!" as his own catachphrase but Emeril beat him to it. The caveman runs off but then encounters a sabre-tooth Amy Winehouse. She pulls a bottle of tequila from her beehive hairdo and empties it in one gulp. She then belches in the caveman's face for a full minute of screen time. She pulls out her Mac laptop and shows her Facebook page when predicts that the world will end on August 29, 2008 unless he can return the crystal skull to the altar.
Cut to August 29, 2008. The hero of the movie, Will, wakes up in bed, having dreamt the earlier scene. He says he wishes he hadn't taken all that Ambien. Cut to a giant empty bottle of Ambien. Some people have suggested this was Jason Friedberg and Aaron Seltzer taking a cheap shot at Heath Ledger's death. I don't think that is the case because if they were, the line of dialogue would have been "I shouldn't have taken all that Ambien just like Heath Ledger". It will become apparent early on that each joke will be spelled out for the viewer. Every third line of dialogue is either "Look, it's ____________!" or "I am _________!" So Will looks at the calendar and sees that it is August 29, 2008. His girlfriend, Amy, is in bed with him. She scolds him for refusing to make a commitment and tells him that she has been cheating on him with Flava Flav. Flava Flav jumps out from underneath the covers and says "I am Flava Flav". Amy gets up and tells Will that he either commits or she is leaving him and taking the midget, too. Will tells her to come to his Super Sweet 16 birthday party, even though he is 25.
At the party, Will runs into a really woman and then somebody who is pointed out to be Dr Phil even though he doesn't look much like him. He says he is depressed because he never knew his father (important plot point). Calvin, Will's best friend, is at the party shaving somebody's eyes out. Anton Chigurh shows up and flips a coin, saying "call it, friend-o". It lands on tails so Chigurh cattle-bolt the sleeping guy between the eyes. Juney and Paulie Bleeker are playing a guitar and singing to each other. He sings that she could get an abortion. She sings back that she already arranged for Brangelina to adopt the kid. Then for some reason she hits him on the head with a guitar. Calvin's girlfriend, Lisa (Kim Kardashian), then shows up and points out that two party crashes are trying to steal booze. It's Jonah and McLovin, only here he is McLover. He says "I am McLover" a lot. Calvin is unable to see this because for some reason there is a giant slab of beef in the way. Carmen Electra shows up, dressed and tattooed like Angelina Jolie's character in Wanted and tells him to curve the bullet to take out the party crashers. Lisa warns her to stay away from her man. Calvin then has a five-minute daydream of Carmen Electra and Kim Kardashian wearing tight spandex and wrestling with each other.
Back in reality, Calvin fires several times, but instead hits Dr Phil, then Anton Chigurh and then Paulie Bleeker. He fires one more time and this time successfully curves the bullet. The bullet "curves" right around Carmen Electra's head and pegs her square in the eyes. Nobody in the party takes any notice that four people were just gunned down. Amy shows up at the party with her new boyfriend, a Calvin Klein model. Juney dresses him down with a protracted "clever for clever's sake" ramble. She pours some vodka into a bottle of Sunny D and chugs the whole thing so her baby can get drunk. The party then breaks out into a High School Musical, which goes on for about five minutes. The song is joined by Justin Timberlake and Jessica Simpson. They all break out into the Souljah boy dance.
Then the room starts shaking. They turn on the radio and hear that it is the end of the world. The news announcer reports that "the ghetto has been wiped out". The white guests act don't care but a group of stereotypical gangstas (who were never seen at the party until now) get upset. Everybody flees the party. There is panic in the street. And by panic, I mean that the camera shakes a lot while a few dozen extras run around Styrofoam meteors and abandoned cars. A bunch of underwear models are running away scared. One of them remarks that she crapped herself. Lisa points out that a meteor has killed on Hannah Montana. Taking a queue from Monty Python and the Holy Grail's "I'm not quite dead, yet" bit, she pops back alive a few times first to plug her new album and then to reveal that she is Miley Cyrus. Will says they have to go to the museum where Amy is working. Funny, I thought she was at the party with her Calvin Klien underwear model. Either I nodded off during an important plot point or continuity is not this movie's primary concern.
Then the street starts to freeze over a la The Day After Tomorrow. They seek refuge in an empty warehouse. Empty except for the four Sex in the City gals. They are made up to look hideous. Carrie Bradshaw is played by a man. They claim that this is their warehouse and start a fight. Juney steps up saying "she never backs down". Carrie and Juney fight with Carre punching Juney repeatedly in her pregnant belly. Juney strikes back with the Zohan roundhouse kick. This is followed by Juney's unborn fetus apparently sliding out her uterus to deliver a baby round house kick. "Eat my placenta" shouts Juney. The four Sex in the City girls run off. The main characters suddenly remembered that it was supposed to be freezing out and they need to strip bare and huddle to stay warm. As they are undressing, Juney's water breaks spraying the others with amniotic fluid. Yet, she does not give birth which is what usually happens when a pregnant woman's water breaks.
While they are asleep, Will has a dream of happier times with Amy. He tells her he is a Jumper and proceeds to teleport around the room. He teleports under her dress. Then he teleports himself back to Narnia where he gets impaled on Prince Caspian's sword. He wakes up and for some reason shows everybody his butt crack which goes up halfway up his back. The camera starts shaking, implying an earthquake. They step outside and see a cop trying to calm people. A meteor strikes (off screen) and he is pelted with severed heads, arms and legs. He runs off. They see Hancock asleep on a park bench. A boy wakes him up and tells him to do something about the disasters. Hancock says "Aw, hell naw" and flies off, hitting his head on the lamp post. Another meteor lands and kills Lisa. Calvin begins to mourn his dead girlfriend but then an Enchanted Princess emerges from the sewer. She is hit by a taxi. She's unhurt and tells them she's not really a princess but a drug addicted prostitute. Her prince, who is really her pimp, also emerges from the sewers and challenges everybody to a duel. The duel is really a five-minute dance off. The effeminate prince does ballet while Juney spins on her pregnant belly. The dance-off is interrupted by a twister. The prince runs back into the sewer. First, Iron Man shows up. In another steal from Monty Python and the Holy Grail, a cow lands on top of him. Then Hellboy shows up. A cow lands on top of him. Then Bruce Banner shows up telling the twister that it wouldn't like him when he's angry. He turns into The Incredible Hulk. His pants blow off right before a cow lands on top of him.
They seek refuge in another warehouse. Enchanted Princess tries to nourish herself by eating glass. Blood pours from her mouth. Calvin gets a call from his "shoe phone". He takes off his shoe phone to answer but didn't realize he had stepped in dog poop earlier. He inadvertently rubs it all over his face. It is Lisa's mother calling. Calvin informs the mother her daughter is dead, but if it's any consolation, he's now hooked up with a prostitute who is willing to do anything. Then Alvin and the Chipmunks show up. They sing a Christmas song. Then a disco song. Then some thrash metal song with the lyrics "worship the devil, blood and intestines" over and over agian. It turns out they are rabid chipmunks. One of them bites Will in the ballsack. The others tear into Juney's back, ripping out her spine. The others are glad to be rid of her. The Enchanted Princess announces for no reason that she has a yeast infection and proceeds to pull a loaf of bread from her crotch.
They flee the warehouse and see Batman urging everybody take the last shuttle out of the city. When they realize that it is after 9 and they missed the shuttle, Batman blames himself for wasting all that time surfing Amazon. He launches his grappling hook with gets attached to the rear bumper of a car. He gets dragged away. The gang find their transportation by carjacking Speed Racer. The Enchanted Princess unloads a couple of clips into his head. They find Michael Jackson in the trunk of the car with the little boy and the chimp. They arrive at the museum and find Amy impaled by a statue with a spear that had fallen on top of her. Calvin suggest knocking her out before removing the spear so it would be less painful. They strike her repeatedly over the head but fail to knock her out. So they just pull the spear out anyway. They then realize that the museum had come alive. Amy tells them that they need to return the crystal skull in order to put an end to the disaster. She pulls it out from her crotch. As they make their way to the altar of the crystal skull, Will and Amy are ambushed by Beowulf. He says "I am Beowulf" a lot. He is also completely naked. They then proceed to go over every single "I'm not gay" joke that went unused in Meet the Spartans, although they neglect the obvious Larry Craig "wide stance" reference. Calvin and Enchanted Princess run into Kung Fu Panda. Calvin gets hit a few times in the balls. Enchanted Princess gets her wig knock off revealing that she is actually a tranny. Kung Fu Panda kills them both with a katana.
Will and Amy, having defeated Beowulf makes their way to the altar of the crystal skull. They see a shadow of who they think is Indiana Jones but it turns out to be Tony Cox, the black dwarf from Bad Santa. Black dwarf Indiana Jones tells Will that....he is his father, thus bringing closure to that very crucial plot point mentioned earlier. He cracks his whip and swings across the room, but gets caught in a ceiling fan which throws him out of the window. Will tries to swing across the room, despite Amy pointing off that there is nothing he needs to swing over. He returns the crystal skull to the altar and the disasters come to an end. Later, Will and Amy are shown being married by the Love Guru. He does the "pickle/tickle" shtick that Mike Meyers did in that movie. Will breaks out his guitar and then begins to sing "I'm Dating Matt Damon". Why they changed it to "dating" instead of just saying "F***ing" and then bleeping it out like they did on the Jimmy Kimmel show is beyond me. This acts as a curtain call for all the characters in the movie. The Hulk sings "I'm Dating Hellboy". Batman sings "I'm Dating Iron Man". Anton Chigurh sings "I'm Dating Amy Winehouse". Michael Jackson sings "I'm Dating Alvin and the Chipmunks". The movie ends with Alvin and the Chipmunk as a cow lands on top of them.
Random disasters have been striking the planet and the only way to put a stop to them is to return the crystal skill back to some altar. Both the crystal skull and the altar are located in the same museum. After an hour of running into characters from movies that came out this past summer, plus the occasional actual disaster, the main characters reach the museum and return the skull to the altar.