It is the first day of school, 1989, and seventeen-year-old Veronica Sawyer is frustrated with the hellish competitive social hierarchy at Westerburg High School, where nerds and underclassmen are pushed around by brutish jocks like Ram Sweeney and Kurt Kelly. After trying to defend her best friend, the cheerful, overweight Martha Dunnstock (cruelly renamed "Martha Dumptruck" by Kurt), Veronica longs for the days of elementary school when life was simple and everyone was friends. She wishes desperately to be above the drama, but there is only one elite clique who can do that: the Heathers, the three most beautiful, most popular girls in school: the weak-willed head cheerleader Heather McNamara; the bulimic, personality-lacking yearbook committee head Heather Duke; and the "mythic bitch" queen of the school, Heather Chandler. When Veronica uses her talents as a forger to get the Heathers out of detention, Chandler recognizes her potential and gives her a make-over, elevating her to a member of their inner circle ("Beautiful").
Veronica soon realizes that popularity is a double-edged sword when Heather Chandler discovers that Martha has had a crush on Ram Sweeney since he kissed her in kindergarten. She orders Veronica to forge a romantic note from him and give it to Martha. Veronica tries to stop them but backs down when the Heathers threaten to destroy her social life ("Candy Store"). Their threats are witnessed by a mysterious, trenchcoat-wearing, Baudelaire-quoting new kid, Jason "J.D." Dean, who criticizes Veronica for betraying her friend in exchange for popularity. Ram and Kurt take the opportunity to pick a fight with him, and he unexpectedly fights back and defeats them. Watching the fight, Veronica finds herself attracted to the stranger ("Fight for Me"). At Veronica's house, Chandler ridicules her for being into someone below her social status and subtly insults her parents, who aren't sure they like their daughter's new friends ("Candy Store Playoff").
Veronica meets J.D. again in a 7-Eleven on her way to Ram's homecoming party. They hit it off, and he flirtatiously extols the virtues of the Slurpee, explaining he uses the brain-freeze to numb the pain of his troubled relationship with his father, the absence of his dead mother, and his nomadic lifestyle ("Freeze Your Brain").
Ram and Kurt's macho fathers leave for a fishing trip, roughing their sons up on the way out the door in a similar fashion to the way their sons treat the kids at school. With his parents gone, Ram starts the party, which quickly grows out of control as Veronica gets increasingly drunk ("Big Fun"). Martha shows up, thinking Ram invited her because of the note, but is cruelly rebuffed. The Heathers try to prank her by dressing up a pig-shaped piñata to resemble her, but Veronica stops them and throws the piñata in the pool. She angrily resigns from the Heathers, but Heather Chandler refuses to allow her to walk away and threatens to ruin her reputation. In response, the inebriated Veronica vomits on Heather's clothes, enraging her, and the frightened students turn their backs on her. Feeling she has nothing to lose now, Veronica breaks into J.D.'s bedroom through the window and seduces him, losing her virginity in the process (“Dead Girl Walking").
After having a nightmare about Chandler tormenting her ("Veronica's Chandler Nightmare"), Veronica decides to go to her house to apologize, with J.D. tagging along. Heather orders Veronica to make her a hangover cure, and J.D., apparently jokingly, suggests putting toxic drain cleaner in it as revenge. Veronica tells him to stop and he apologizes, kissing her. Still dazed from the kiss, Veronica grabs the wrong cup. J.D. notices the mix-up but says nothing as Chandler humiliates Veronica, rejects her apology, drinks the drain cleaner, and dies. Fearing no one will believe it was an accident, Veronica panics until J.D. spots Heather's copy of The Bell Jar. He convinces Veronica to forge a suicide note. In the process, she makes Heather sound more deep and complex than she actually was, gaining her sympathy from the entire school and inspiring ex-hippie teacher Miss Fleming to start a school-wide campaign to prevent teenage suicide ("Me Inside Of Me").
With Heather Chandler dead, Heather Duke breaks free of her subservient status and assumes control. Veronica and J.D. watch her give sob story interviews on multiple news channels (and in multiple languages) at J.D.'s house, where Veronica witnesses first-hand J.D.'s tense relationship with his father, demolitions expert Big Bud Dean. Veronica's displeasure at the new status quo is equaled only by that of Chandler herself, who appears as a ghost to berate Veronica from beyond the grave. Veronica gets a call from Heather McNamara, begging her to come to the cemetery, and when she gets there, she discovers the Heathers have locked themselves in a car, trying to fend off a drunk Kurt and Ram. It emerges that they escaped date-rape by the intoxicated football players, who are desperate for sexual relief, by telling them that they can have Veronica. The boys aggressively beg her to have sex with them ("Blue"), but she escapes by giving them more alcohol until they pass out. The next day, Veronica discovers that Heather Duke has taken on Heather Chandler's role of leader, as she takes Heather Chandler's red scrunchie (a symbol of her power) from her locker, and that Ram and Kurt have told everyone that Veronica had sex with them ("Blue (Reprise)"). She is branded a slut by the other students ("Blue Playoff"). Kurt and Ram then beat up J.D. and Veronica starts to cry.
J.D. comforts Veronica and enlists her help in a plan to get revenge on the two jocks. She lures them into the cemetery with the promise of making their lies about her come true, where J.D. explains that they will shoot them with special "Ich Lüge" (German for "I Am Lying") bullets which cause temporary unconsciousness, putting them out long enough for cops to find a forged suicide note proclaiming they're gay lovers. Once the jocks are in position, J.D. shoots Ram, but Veronica misses Kurt, who runs into the woods, pursued by J.D. As Veronica realizes Ram is dead and the bullets are real, J.D. shoots Kurt down in cold blood, and proclaims his undying love to a horrified Veronica ("Our Love is God").
At Ram and Kurt's joint funeral, a distraught Veronica reflects on Ram and Kurt, musing that they could have potentially outgrown their immaturity, but their lives were cut short before they were given the chance ("Prom or Hell?"). Their fathers unexpectedly decide to accept their sons' homosexuality, even more unexpectedly reveal their own past love affair during a fishing trip, and vow to work towards making the world a more tolerant place ("My Dead Gay Son"). Seeing this as a sign their murders are making the world a better place, J.D. tries to convince Veronica they should make Heather Duke their next target. She refuses, provoking a furious rant from J.D. about the way society creates pain and misery. Sensing the deeper pain driving his fury, Veronica asks J.D. how his mother died, and learns that he watched her commit suicide by walking into a library his father was demolishing just before it was blown up. Veronica begs him to give up trying to change the world through violence and live a normal life with her ("Seventeen").
When J.D. leaves, Heather Chandler's ghost appears once more doubting he really changed. Martha asks Veronica for help breaking into J.D.'s locker, as she suspects he murdered the football players, insisting Ram couldn't be gay because of the love note he wrote her. Veronica realizes that if Martha found anything incriminating she would become J.D.'s next target and also fears that her own role in the killings might be discovered. Listening to ghostly Heather Chandler's advice, Veronica drives Martha away by confessing she wrote the note and that Ram thought she was a loser. Martha runs off in tears.
School guidance counselor Pauline Fleming holds a televised therapy assembly in order to aid the student body and prevent any more suicides from happening, and coincidentally to promote Fleming's controversial therapeutic techniques on live television ("Shine a Light"). Heather McNamara is the only one to step forward, confessing she's thought about killing herself due to the overwhelming peer pressure she faces every day ("Lifeboat"). Duke mocks McNamara and whips the other students into a frenzy. Veronica lashes out at Ms. Fleming for taking advantage of the publicity and not protecting McNamara, and in her rage, she confesses to the murders. No one believes her, thinking she is just desperate for attention. She follows McNamara to the school bathroom, where she catches her attempting to overdose on a bottle of sleeping pills ("Shine a Light (Reprise)"). Veronica stops her in time and comforts her. J.D. tries to talk Veronica into killing Duke again, and Veronica realizes he is carrying around a loaded gun. Realizing how unstable he is, Veronica breaks up with him. They argue, and he accidentally points the gun at her. She storms out as the other students (including Heather McNamara) reveal that there is going to be a pep rally later that night ("Hey Yo, Westerburg").
J.D. confronts Duke with evidence that she and Martha were friends when they were children, and blackmails her into getting all the kids at school to sign a petition declaring a holiday in remembrance of the victims of suicide. Martha, feeling unnoticed and mourning Ram, tries to commit suicide by jumping off a bridge ("Kindergarten Boyfriend"). She survives with a few broken bones, and her suicide is billed as a failed attempt to imitate the popular kids. Veronica rushes to the hospital as the ghosts of Kurt, Ram, and Heather Chandler taunt her with the realization that she has become as awful as Chandler ("Yo Girl"). When she returns home her parents confront her, telling her J.D. has told them she is suicidal, and she realizes J.D. plans to make her his next victim. He breaks into her room, wielding a gun, as she barricades herself in the closet. Increasingly unhinged, he tells her he's changed his mind about killing her, believing the solution to their problem is to kill the student body that's brainwashed her. He reveals that the petition, signed by every student at Westerburg, was actually a disguised suicide note, and he plans to blow up the school while everyone's at a pep rally, making it look like a mass suicide. Growing impatient, he breaks open the door, and finds Veronica dangling from a noose. Grief-stricken, he rushes out to complete his plan in her memory ("Meant to Be Yours").
Veronica, however, has faked her suicide, and grabs a croquet mallet to put an end to J.D.'s madness, even if she has to die in the process. ("Dead Girl Walking (Reprise)"). She confronts him as he's setting up the bomb in the boiler room underneath the gym. She begs him one final time to stop, but he refuses to listen, and she attacks him. In their struggle, his gun goes off, and J.D. collapses with a bullet in his gut. Having no idea how to disarm the bomb, Veronica takes it out to the empty football field, intending to save the other students by sacrificing herself. J.D., still alive, follows her and convinces her to let him take the bomb instead ("I Am Damaged"), asking her to do something good with her life. The bomb goes off, killing J.D. and leaving everyone else unharmed.
Returning to the school singed but alive, Veronica takes the red scrunchie from Heather Duke and declares to the student body that the era of constant ridicule and belittlement is over. Veronica invites Martha and Heather McNamara to hang out, rent a movie, and simply be kids for a little while before their childhoods are over ("Seventeen (Reprise)").