It has been two years since the horrific events in Woodsboro, California. The young survivors - Sidney Prescott and Randy Meeks - have decided to forget their traumatic experience and move on with their lives. Together, the two friends enroll as freshman at Windsor College, a midwestern university in Ohio. As for news reporter Gale Weathers, she has cashed in on her bloody ordeal by writing a best-seller on the event, which has inevitably been turned into a movie called Stab. And coinciding with the film's release are the brutal deaths of two college seniors - Maureen Evans and Phil Stevens.
Sidney becomes aware of the two deaths a day after and begins to fear that someone is continuing the deadly legacy of Billy Loomis and Stuart Macher. During all of the media attraction, she finds that Gale has arrived to interview her, while Dewey Riley has arrived to protect her. Later that night, Sidney escapes a deadly attack from the masked murderer and the campus police finds that another college student - Cici Cooper - has been found murdered. The next day, Gale and Dewey assist Chief Louis Hartley of the campus police in investigating the new series of murders. What they discover is a copycat killer repeating the events of Woodsboro, who is deciding to finish what was started.
After Randy is found dead, the campus police take Sidney to a safe haven far from Windsor. But when the killer shows up along the way, Sidney desperately searches for help, as does Gale when she witnesses the killer stabbing Dewey repeatedly in the back. When Sidney finally reaches Windsor, she discovers that Mickey - one of her friends - is the campus killer! Apparently, the psychotic film student wanted to be the first serial killer to walk away as an innocent vicitim after blaming his actions on the movies. And when the second killer - Debbie Salt - shows up with Gale at gunpoint, Sidney recognizes her as Mrs. Loomis, Billy Loomis' mother! After Mickey is unexpectedly gunned down by his partner, Cotton Weary shows up and saves Sidney's life by killing Mrs. Loomis, who tried to avenge her son's death.
In the aftermath, the college campus of Windsor was brought back to its peaceful state. Gale survives her wounds from the deadly confrontation and dumps her tabloid ways after she discovers that Dewey managed to survive as well! As for Sidney, she decides to give Cotton his chance of fame so that he may finally clear his name and piece back together his life, after she had put him in prison for a year. It is finally over... for now.