Scream VI

One year after the Woodsboro killings orchestrated by Richie Kirsch and Amber Freeman, Blackmore University professor Laura Crane is catfished and murdered by her student Jason Carvey wearing a Ghostface costume because of him blaming her for failing. Jason plots with his roommate Greg to kill sisters Sam and Tara Carpenter to finish the "movie" that Richie and Amber wanted to make. However, Jason receives a call from a different Ghostface, who has killed Greg and subsequently stabs Jason to death.

Sam and Tara now live in New York City, with Tara attending Blackmore University alongside fellow survivors Chad and Mindy Meeks-Martin, their roommate Quinn Bailey, Mindy's girlfriend Anika Kayoko, and Chad's roommate Ethan Landry. Sam attends therapy with Dr. Christopher Stone and has become a public pariah because of an online conspiracy theory that she was the true mastermind of the recent killings. Quinn's father, Detective Wayne Bailey, calls Sam in for questioning as her ID was found at the scene of Jason's murder, along with a Ghostface mask worn by Richie and Amber. On the way to the station, Ghostface calls Sam from Richie's phone, who then attacks Tara and kills multiple bystanders in a bodega, and leaves behind another Ghostface mask worn in the 2011 Woodsboro killings.

At the NYPD police station, the sisters meet with FBI special agent Kirby Reed, a survivor of the 2011 killings, and reporter Gale Weathers, who has since written a new book on the previous Woodsboro killings despite promising the Carpenter sisters that she would not. She tells them she spoke to Sidney Prescott and that she has gone into hiding to protect her family. Dr. Stone is murdered by Ghostface, who steals Sam's file and leaves behind a mask worn in the Hollywood killings. Mindy theorizes that the killer is following the rules of film franchises, specifically the rule that anyone can die while the franchise will still continue. From his window, Sam's boyfriend Danny witnesses Ghostface stabbing Quinn in Sam and Tara's apartment before attacking the group and killing Anika, leaving behind a mask worn in the Windsor College killings. Gale takes the group to an abandoned theater she found while investigating, which has been set up as a shrine to the Ghostface killers, featuring many items of evidence related to previous massacres now displayed like film props.

Ghostface calls Gale at her apartment and torments her about the death of Dewey Riley before killing her boyfriend and attacking her. Sam and Tara arrive just in time to stop Ghostface from killing Gale, who is taken to the hospital. The group agrees to meet Kirby at the theater to trap Ghostface. Mindy is stabbed by Ghostface on the train. At the theater, Sam sees a hallucination of her father, original Ghostface killer Billy Loomis. Taking his knife from the original murders, she realizes they have been locked inside. Two Ghostfaces appear and attack Chad. Wayne and Kirby both arrive with guns drawn and he shoots her, revealing himself as a third Ghostface and the mastermind. His accomplices are his children, revealed to be Ethan and a still-alive Quinn, who faked her death to ease suspicion. They reveal their motive is to take revenge on Sam for killing Richie, who was their brother and Wayne's first-born son. They defamed Sam online and infiltrated her life with the intent of killing her. Sam and Tara ultimately gain the upper hand and fight them off, with Tara stabbing Ethan and Sam killing Quinn while briefly rendering Wayne unconscious. Sam then dons her father's Ghostface costume, taunts Wayne with a phone call, and stabs him to death. Ethan resurfaces, but Kirby smashes a television set over his head, killing him.

Sam agrees to let Tara live her life more independently, and Tara agrees to go to therapy. As Mindy, Chad, and Kirby are taken to the hospital, Sam stares at her father's Ghostface mask before discarding it and following Tara and Danny into the city.