On the fifteenth anniversary of the original Woodsboro massacre pulled off by Billy Loomis and Stu Macher, high school students Jenny Randall (Aimee Teegarden) and Marnie Cooper (Brittany Robertson) are attacked and brutally killed by a new Ghostface.
The following day, survivor Sidney Prescott (Neve Campbell) returns to Woodsboro to promote her new book with her publicist Rebecca Walters (Alison Brie). Sidney becomes a suspect in the murders after evidence is found in her rental car, and she must stay in the town until the murders are solved. Her cousin, Jill (Emma Roberts), who is dealing with the betrayal of her ex-boyfriend, Trevor Sheldon (Nico Tortorella) gets a threatening phone call from Ghostface, as does her friend Olivia Morris (Marielle Jaffe). Jill and Olivia, alongside their friend Kirby Reed (Hayden Panettiere), are questioned about their calls by Dewey Riley (David Arquette), who is now the sheriff of the town, and one of his deputies, Judy Hicks (Marley Shelton). Dewey's now-wife, Gale Weathers Riley (Courteney Cox), is struggling from writer's block, attempting to get in on the investigation to reignite her inspiration, much to Dewey's annoyance.