The next day, Cindy Campbell (Anna Faris), meets up with her boyfriend Bobby Prinze (Jon Abrahams) and her friends, Brenda Meeks (Regina Hall), Ray Wilkins (Shawn Wayans), Greg Phillipe (Lochlyn Munro), and Buffy Gilmore (Shannon Elizabeth). Various news teams, including hack reporter Gail Hailstorm (Cheri Oteri), converge on the school in the wake of Drew's death. Gail hooks up with Buffy's mentally disabled brother "Special Officer" Doofy (Dave Sheridan), hoping to milk the facts out of him. One day, while Cindy is in class, she is left a note indicating knowledge about an incident exactly one year prior, in which she and her friends accidentally killed a man during a wild car ride and threw him into the pier. Unwilling to face incarceration, the next day a series of increasingly bizarre events take place. Various members of the group receive threatening notes from Ghostface and are rapidly dispatched, but most remain steadfastly oblivious to the rising body count. At Buffy's beauty pageant, Greg is killed, (to which none of the audience reacts to Buffy's cries for help as they believe she is doing a dramatic reading) which she negates after winning due to her genuine performance. The killer then attacks Cindy in her house. She tries to call the police, but the killer escapes. Bobby arrives at her house but a knife and a pair of gloves leads Cindy to believe that Bobby is the killer. The police arrest Bobby, but Cindy receives a threatening phone call from somebody else claiming to be the killer, so he is released the next day. Buffy is confronted by Ghostface in the locker room, but believing to be a prank, sarcastically plays along with it (following all of the horror clichés) until Ghostface decapitates her (though she continues to mock him afterwards.) Later, at the movies, Ghostface sticks his penis through Ray's head when he puts his ear next to a glory hole, seemingly killing him. Ghostface then attempts to dispose of Brenda during a showing of Shakespeare in Love, but the moviegoers, agitated with Brenda's constant interruptions during the movie, stab her repeatedly, killing her.

Cindy throws a house party, hoping for safety in numbers. During the party, a drunk Cindy finally lets Bobby have sex with her; They make out (twisting up their tongues), and Bobby takes off her pants (bats fly out, with Cindy stating "I guess it's been a while") no longer making Cindy a virgin. Ghostface unexpectedly appears and stabs Bobby, before disappearing quickly. Cindy gets a gun from a drawer near the entrance, Bobby follows and she tends to his wounds. Shorty (Marlon Wayans), Brenda's stoner brother, comes up from the basement, (where Ghostface had been smoking with him and his friends) and informs them that the killer has murdered everybody in the house. Bobby takes the gun and shoots Shorty, revealing that his wound was an elaborate ruse. Ray arrives on the scene, whereupon Bobby claims his cause for the crimes to be because Cindy refused to him sex, and he was homosexual with Ray, despite Ray's insistence to the contrary. They announce their plan to kill her father and frame her sister. Ray and Bobby also plan to make themselves look like heroes by giving each other stab wounds to indicate they fought back. But, Ray stabs Bobby repeatedly and accidentally kills him, while making a tirade about his favorite show, The Wayans Bros., being cancelled. However, the real Ghostface abruptly arrives and stabs Ray, who collapses on top of Bobby in the Doggy style position. The killer attacks Cindy, but she successfully subdues him by employing moves copied from The Matrix and kicks him through a window. Nonetheless, Ghostface vanishes before the police arrive.

At the police station, Cindy and the local sheriff (Kurt Fuller) realize that Doofy, the only one who knew about the car accident, was actually faking his disability and is the true killer. Unfortunately, Doofy has already escaped with Gail Hailstorm. Upon finding his discarded disguise in the street, Cindy begins screaming, only to be hit by a car.

As the credits roll, Shorty, parodying the rules of a trilogy in Scream 3, explains via videocassette that he may be in prison or deceased, but provides rules for surviving such a situation, which turn out to be instructions for surviving a snatch-and-run.

Reception
The film received mixed reviews from critics. On Rotten Tomatoes, 53% of critics gave the film a positive review based on 111 reviews.

Joe Leydon of Entertainment Weekly gave the film a positive review, remarking that the film was "unbounded by taste, inhibition or political correctness" and that "the outer limits of R-rated respectability are stretched, if not shredded" by the movie. By contrast, Roger Ebert did not find the film as innovative, saying that the film lacked "the shocking impact of Airplane!, which had the advantage of breaking new ground." However, Ebert did give the film 3 stars out of 4, saying it "delivers the goods", calling the film a "raucous, satirical attack on slasher movies."

Bob Longino of The Atlanta Journal-Constitution felt that the film's crude humor detracted from the film, saying that Scary Movie "dives so deep into tasteless humor that it's a wonder it landed an R rating instead of an NC-17." Other reviewers, such as A.O. Scott of The New York Times, argued that the jokes were "annoying less for their vulgarity than for their tiredness." Scott remarked in his review, "Couch-bound pot smokers, prison sex, mannish female gym teachers, those Whassssup Budweiser commercials -- hasn't it all been done to death?". The film was the first to score zero (out of 100) from the Christian ChildCare Action Project, which rates films based on their perceived suitability for minors.