Warning: Wikipedia contains spoilers
Sydney tries to sort through the trauma of being attacked and, because of circumstantial evidence, points an accusatory finger at her boyfriend Billy (played by Skeet Ulrich). She goes to stay at the home of her friend Tatum (played by Rose McGowan) and Tatum's brother Dewey (played by David Arquette), a local policeman. While there she receives a call from the killer, and since Billy couldn't have made the call from prison, he is released.
As if all of this weren't enough, Sydney must deal with the scandalization of her own attack by ambitious local television newswoman Gale Weather (played by Courteney Cox.) Gale is also responsible for a tell-all book revealing the promiscuous affair that Sydney's mother had with her convicted killer, Cotton Weary (played by Liev Schreiber.) When the school principal is murdered, some of the local students decide to throw a party. (Attending are all of the above mentioned teens plus Randy ((played by Jamie Kennedy,)) a horror movie buff, and Stu ((played by Matthew Lillard.)) ) The party quickly becomes a bloodbath as the killer invades, quickly dispatching of Billy and Tatum.
In the interim, Gale, who senses a potential major news story, is lurking around outside with the help of Officer Dewey (whom she has flirted into her confidence.) When they suspect trouble, they split up. Gale heads to her newsvan, where she finds her cameraman slaughtered. Suddenly being chased by the killer herself, she tears away in the newsvan only to crash into a tree.
Meanwhile, Sydney, who has discovered her murdered friends, is prowling around the outside of the house looking for help. When she finds none, she heads back to the front door only to find Dewey stabbed in the back. She heads inside the house and is confronted by both Randy and Stu. Not knowing who to trust, she slams the door in their faces. Suddenly Billy appears, bloodied but alive...until it is revealed that his attack was staged. Thus Sydney realizes the truth: Billy is the murderer. She opens the front door to warn her other two friends, and randy stumbles in only to be knocked unconscious by Billy. Then Stu appears, and the ultimate truth presents itself: they were working together.
It turns out that the two boys are actually responsible for the murder of Syndey's mother one year ago. Billy concocted the scheme when he discovered that Sydney's mom was having an affair with his father. They framed Cotton Weary, with whom she was also having an affair, and to add insult to injury have murdered everyone Sydney loves. They reveal that they have kidnapped her father and that they intend to frame him for all of the recent murders. However, they go overboard when they begin to slash at each other in an attempt to be wounded enough to claim that they "just escaped death" when Sydney's father attacked them. Sydney slips away, and manages to kill Stu.
At the last minute, Gale Weathers appears and Billy knocks the gun away from her because she forgot to take off the safety. Sidney retrieves the gun and blows Billy away. Shortly thereafter, Randy also regains consciousness, and the police arrive, reviving Deputy Dewey. Everyone else is dead. A huge amount of loss of life has lead to a revelation for young Sydney, who must now free the man she thought responsible for the death of her mother.
The film featured numerous in-jokes and references to other horror projects. (An example: a character references that the first "A Nightmare On Elm Street" film was good but "the rest of them sucked;" Scream director Wes Craven directed the first Elm Street film.) Also, the characters in Scream all make clear their awareness with teen slasher and horror films, which makes them unique in the way they deal with what happens to them. The film opened to huge critical acclaim and financial success, and spawned two sequels and a series of slasher movies (and spoofs), among them: