During a senior calculus class at Covington High, senior student Katelyn Ogden inexplicably explodes, spraying the surrounding students and classroom with blood. The police take the class into custody during an investigation, but aside from ruling out an attack, are unable to determine the cause of the explosion.

During custody, senior student Mara Carlyle suggests to the class that it could happen again, a sentiment taken seriously by her peers. Afterwards, an unknown person texts her, claiming to have had a crush on her for multiple years: Mara promptly asks for the texter not to send a dick pic, to which the individual responds with a picture of Richard Nixon.

Following Katelyn's funeral service, Mara gets high on mushrooms purchased from school dealers, Jenna and Joe Dalton, and goes for tea with her best friend Tess; fellow student Dylan approaches the pair and reveals himself to be the unknown texter with said crush on Mara. Dylan explains how he had begun thinking of life and how quickly it could end, and upon hearing Mara's suggestion of the incident repeating itself, realized that he needed to take action.

They begin seeing one another and attend a school football game and house party, although each is cut short when a jock, Perry Love, and drink server, Cranberry Bollinger, explode, respectively, sending the attendees into a panic. Classes are cancelled for a while, and people begin to dub the explosions as "The Covington Curse". The incidents attract the attention of numerous government agencies, who place FBI Agent Carla Rosetti on the case; she enlists Mara and Tess as aid.

While investigating the possible involvement of drugs, Mara goes for a drive with the school dealers, the Dalton twins; they explode and the car crashes. Dylan arrives and consoles a dazed Mara, before federal agents arrive in protective suits and detain them. The entire senior class is placed in observation while the government devises a "Snooze Button" pill to "cure" the students, during which multiple students explode. Realizing they should live like every day might be their last, Mara and Dylan continue seeing each other, pursuing a hedonistic lifestyle; they have sex and dance to 80s music in an old barn.

School resumes for the senior class, although the townspeople begin to fear the students and Agent Rosetti inadvertently admits to Mara that the explosions may not yet be over. While demonstrating the supposed effectiveness of the pill at a school seminar, a student explodes, triggering a chain reaction of explosions in the classroom. Dozens of students explode during the ensuing rampage, whereas Mara and Dylan are separated by the mob in a struggle to escape the building. Mara exits through a side entrance with ease and reunites with Dylan, who tells her he's glad she's still here and then explodes, injuring Mara in the process.