The full plot of Scream 6 follows two Ghostface killers through the opening, then a larger conspiracy that ends in an abandoned theater. The opening murders of the professor and the two students are carried out by two different people in Ghostface masks, which sets up the film's habit of showing more than one killer at once.
In New York, Sam and Tara Carpenter try to move on while living with Mindy, Chad, Quinn, Anika and Ethan. Ghostface starts hunting the group, and the killer also targets a therapist who knew Sam. Sam herself is blamed for some of the crimes. Gale Weathers joins the survivors and leads them to a hidden, abandoned theater that works as a shrine, filled with relics from past Ghostface killers.
The violence is staged in public places. Gale is attacked in her apartment, and Mindy is stabbed on a crowded train, while Quinn and Anika are lost along the way. At the theater the group sets a trap, and the killers are exposed.
Quinn's father, a police detective named Wayne Bailey, planned everything, with Ethan and a still living Quinn helping him. They want revenge on Sam for killing Richie, who was their brother. In the fight, Tara stabs Ethan, Sam kills Quinn, and Sam finishes Wayne while wearing the Ghostface costume that once belonged to her own father. Kirby arrives and ends Ethan by smashing a television over his head.
The survivors recover, Sam gives Tara more freedom, and Tara agrees to go to therapy. Sam drops her father's mask and walks off into the city with Tara and Danny Brackett.
