In Westerburg High School in Sherwood, Ohio, Veronica Sawyer is part of a popular but feared clique that also consists of three other wealthy and beautiful girls with the same first name: Heather Chandler, Heather Duke, and Heather McNamara. However, having grown tired of them and longing to return to her old life with her "nerdy" friends, Veronica becomes fascinated with Jason "J.D." Dean, a new student and rebellious outsider, after he pulls out a gun and fires blanks at Kurt Kelly and Ram Sweeney in response to their torture. She later attends a frat party with Chandler, but refuses to have sex with one of the members and vomits on Chandler. In retaliation, Chandler vows to destroy her reputation. J.D. arrives at Veronica's house, and the two have sex outside. They express to each other their mutual hatred of Chandler's tyranny.
The next morning, Veronica and J.D. break into Chandler's house, where J.D. puts drain cleaner in a mug for Chandler but Veronica dismisses his plan. She mixes orange juice and milk together instead, as an attempt to make her vomit and get revenge. However, J.D. hands Chandler the mug with the drain cleaner, killing her. Veronica panics but J.D. urges her to forge a dramatic suicide note in Chandler's handwriting. The school and community regard Chandler's apparent suicide as a tragic decision made by a troubled teenager, making her even more worshipped in death than in life. Duke soon becomes the clique's leader and begins wearing a red scrunchie that Chandler had worn.
McNamara convinces Veronica to go with her, Kurt and Ram on a double date, during which Veronica leaves with an incensed J.D., while Kurt passes out, and Ram rapes McNamara in a field. The following day, the boys spread a false rumor about Veronica performing oral sex on them, ruining her reputation. J.D. proposes that she lure them into the woods and then shoot them with non-fatal bullets. J.D. shoots and kills Ram but Veronica misses Kurt, who runs away. J.D. chases Kurt back towards Veronica and kills him. J.D. plants material next to the boys implying that they were gay, and a note stating the two were lovers participating in a suicide pact. At their funeral, the boys are made into martyrs against homophobia. Although Veronica keeps dating J.D., his behavior increasingly disturbs her. Martha Dunnstock, a frequent target of bullying, pins a suicide note to her chest and walks into traffic. She survives but is badly injured and mocked by her peers. Later, McNamara calls a radio show to discuss her depression; the next day, Duke tells the entire school about the radio call. McNamara attempts suicide by overdosing in the girls' bathroom, but Veronica saves her and tells J.D. that she will not participate in any more killings, breaking up with him.
J.D. blackmails Duke into getting the students to sign a petition that unbeknownst to her is intended to act as a mass suicide note. Later, Veronica fakes her own suicide to manipulate J.D., who assumes she is dead and reveals his plan to blow up the school during a pep rally. The next day, Veronica confronts J.D. in the boiler room while he is planting dynamite. She shoots him and his switchblade cuts the wires to the detonator. J.D. follows Veronica outside with a bomb strapped to his chest, offers a personal eulogy, and detonates the bomb, killing himself. As the students and faculty rush outside to see what had happened, Veronica walks back inside, dirty and disheveled from the explosion. She confronts Duke, takes the red scrunchie, and asserts herself as the new leader. She then invites Martha to spend prom night watching movies together, as Duke watches on.
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