The film starts out with a teenage girl named Casey who is alone at her parents' home for the evening. Whilst in the process of making popcorn, she receives a call from a man. He tells her that he has the wrong number and she hangs up. When he calls again, he asks her what her favourite scary movie is and begins ask her other horror trivia based questions. Initially, Casey plays along with him, but becomes frightened as the game begins to get more sinister. The man on the phone shows Casey her boyfriend, who is tied up outside the house. He informs Casey that if she answers the question correctly, she and her boyfriend will live, but if she answers wrong, she will die.
The man on the phone gives her a trick question about "Friday the 13th", which she answers wrong. Casey looks up to see that her boyfriend has been murdered. Casey panics, hangs up and runs out of the house, but the caller, who is seen wearing a cloak and a mask, catches up with her and kills her. When her parents come home, they discover her body hanging from a tree.
The film then moves onto to a school, where the students are discussing the murders from the night before. Sidney Prescott is a student at the school and is dealing with the anniversary of the death of her mother, who was murdered. She is later attacked by the same killer (who is known as Ghostface) that murdered Casey, but manages to escape. She runs into her boyfriend Billy and as time goes on, she begins to grow suspicious of him. Billy is taken in for questioning after a phone drops out of his pocket around the same time that the killer contacted Sidney.
The events begin to take its toll on Sidney, and she attacks Gale Weathers, a reporter who has written a book about Sidney's mother's affair with her killer. Later, after the school is closed due to the events, the school principal is murdered. The teenagers all attend a party. During the party, Tatum Riley, Sidney's best friend, is killed when she becomes trapped in a garage door trying to escape the killer.
Meanwhile, one of the teenagers, Randy, sits down with the rest of the group and they begin to watch "Halloween", which Randy pauses halfway through to explain the "rules" of a horror movie. The teenagers leave when they hear of their principal's death, leaving Randy alone. Billy, who was upstairs with Sidney, is attacked. Sidney escapes and continues to run when she notices Tatum's body.
Gale and her cameraman Kenny are watching the events of the party hoping for something to happen. Kenny is later murdered by the killer and Gale encounters Tatum's brother Dewey, who is a Deputy sheriff. Sidney later returns to the house and is left with only two potential suspects for the killings - Tatum's boyfriend Stu, and Randy. Both of them insist that they aren't the killers, and Sidney, who is clearly stressed by the situation, rushes inside, shutting the door behind her.
Once inside, she notices that Billy is still alive. He falls down the stairs. He opens the door and Randy runs inside. Randy states that Stu has gone mad, to which Billy replies "we all go a little mad sometimes". He then shoots Randy and licks blood from his fingers, after which he says "corn syrup - same stuff they used for pig's blood in Carrie", indicating that the attack on him earlier was fake.
Sidney learns that Billy and Stu are responsible for the murders. She also discovers that it was Billy that brutally attacked and killed her mum. Sidney asks why and Billy gives her a motive. He tells her that her mother was having an affair with his father, which caused his family to break up. They bring out Sidney's father, who they abducted. Gale shows up and tries to shoot Billy and Stu, but is knocked out.
A violent fight between Billy, Stu and Sidney breaks out, which results in Stu being killed by a television when Sidney pushes it onto him and Billy is shot by Gale, who awakens. Randy, who is still alive, warns that the killer always comes back to life for one last scare. Billy does so and Sidney shoots him, killing him for good.