Wallace, a Black, gay biochemistry graduate student at a Midwestern university, joins his friends at the lakeside pier on a Friday evening in late summer. His father has been dead for several weeks, a fact he has shared with no one. An hour earlier, he discovered that his nematode experiments, months of careful breeding work on tiny worms, have been destroyed by severe contamination that feels deliberate. For the first time in four years, he had been on the verge of a breakthrough.
At the pier, Wallace finds Miller, Yngve, and Cole, fellow graduate students in biochemistry, along with Cole's boyfriend, Vincent. Wallace was the first Black student admitted to their incoming class in over three decades. He and Miller share a fraught history: Miller once made a racially charged comment at a seminar, creating a lasting rift, though both are first-generation college students who felt cowed upon arriving in the Midwest. When Wallace surprises the group by admitting he thinks about leaving graduate school, he realizes the deeper truth: He does not just want to leave the program. He wants to leave his life.
Emma, Wallace's closest friend in the program, a bond formed because neither is a white man in their cohort, arrives with her fiancé, Thom, and finds Wallace near tears at the water's edge. He tells her his father died weeks ago and that he did not attend the funeral. Emma cries on his behalf and impulsively kisses him, his first kiss. Back at the table, Wallace discovers Emma has told the group about his father's death. When Miller gets jalapeño residue in his eyes, Wallace follows him to the bathroom and tenderly rinses them. A charged moment passes between them, and they hold hands until they reach the door.
Wallace and Miller leave the pier together. Miller admits he is not into men but hates the idea of Wallace hating him. At Wallace's apartment, Miller confesses he wants to kiss Wallace, and the encounter escalates. They have sex for the first time. Afterward, Wallace cannot sleep. He compulsively drinks water and vomits it up. Miller finds him and shares that his mother died of cancer two years ago, that she was mean and difficult but that he stayed at her side every day. They have sex again before settling into uneasy rest.
Saturday morning, Wallace goes to the lab. Under the microscope, the contamination is worse than expected: His experimental worm line shows signs of sterility, and recovery will require enormous effort. Brigit, a gifted Chinese American researcher and Wallace's closest lab ally, suggests that Dana, another student, may have sabotaged his plates. Wallace recalls a history of conflict with Dana, who once blamed him for a mistake she herself made, and their adviser, Simone, believed Dana's version. Later, Dana confronts Wallace, accusing him of misogyny and declaring that "women are the new niggers, the new faggots" (96). Wallace, stunned, tells her to leave him alone.
Wallace meets Cole for tennis. Cole reveals he discovered Vincent on a gay dating app and is devastated. Cole also mentions that Yngve is setting Miller up with a woman named Zoe at a dinner party that evening; the news stings Wallace. After their match, Cole confesses he once thought about being with Wallace before Vincent moved to town. Wallace tells him it would have been a mistake and agrees to attend the party.
At the dinner party, Roman, a French student, challenges Wallace about his desire to leave, arguing that Wallace owes the department gratitude and that, given his "deficiencies" and "challenging background" (161), he has better prospects as a Black person if he stays. No one speaks up in Wallace's defense. He smiles through the humiliation, fists clenched under the table. Still stinging, Wallace deliberately reveals to the table that Vincent is on the dating app. The dinner erupts into tears and accusations. Emma confronts Wallace privately, saying his action was selfish: She told their friends about his father to help him, while he exposed Cole and Vincent's problems to hurt them.
Wallace vomits in the bathroom, and Miller takes him upstairs to rest. Miller asks Wallace to tell him about his past. Wallace's narration shifts to first person as he describes his childhood in Alabama: violent storms, his grandparents' oppressive religiosity, sermons warning that wanting men leads to AIDS and death. He reveals that a man who slept on their couch sexually abused him repeatedly as a child. When his mother discovered it, she slapped Wallace and called him a faggot, blaming him. His father grinned and said he hoped the man "had done something good" for Wallace (201). Wallace's mother had herself been raped, and his grandmother told him she "deserved it" (200). He describes a boy in adolescence who had sex with him but beat him violently afterward. He left Alabama for graduate school, determined to seal his past behind him and become someone new.
Wallace wakes alone in Miller's bed at midnight. Alone with Miller downstairs, Wallace keeps trying to leave. Miller confesses his own violence: He nearly killed a boy in Indiana, beating him so severely the boy's heart stopped three times in the ambulance. They have sex again, though Wallace feels disconnected. After Miller falls asleep, Wallace slips out before dawn.
Sunday morning, Miller arrives upset that Wallace left again. At brunch, Cole and Vincent have reconciled, but Vincent publicly scolds Wallace for meddling in their relationship. Miller and Yngve attempt to defend Wallace, but he quietly accepts the blame with practiced contrition. Later, Simone calls Wallace to her office. Dana has accused him of misogyny. Simone tells Wallace she does not see someone who truly wants to be a scientist and asks him to consider whether he wants to stay in the program.
Wallace meets Brigit at the pier and tells her his father died. They cry together. Brigit reveals her own pain, feeling reduced to "the Asian girl" (275) rather than a person. That night, Miller arrives at Wallace's apartment drunk and bloodied from a bar fight after someone called him a faggot. He is angry that Wallace left him twice, that Wallace shared his deepest secrets and then disappeared. The encounter turns violent: Miller grabs Wallace's throat, forces him against the counter, and roughly penetrates him with his fingers before immediately pulling back. Wallace insists he provoked Miller. They fight physically until the violence exhausts itself. Lying in bed, bruised, Wallace tells Miller about his father abandoning him in middle school without explanation. He refuses to give Miller the anger Miller craves, saying Miller wants punishment to feel less like a monster.
In the middle of the night, they cook together. Wallace fries fish, remembering how his father taught him to cook, a rare tender memory. They wade into the lake in the dark, where Miller holds Wallace steady as he floats on his back, learning to swim. Afterward, they sit on the roof of Wallace's building in wet clothes, watching the sun rise as "the world turned over itself, to begin again" (319).
The final chapter flashes back to Wallace's arrival in the Midwest on a hot July day, his first time out of the South. He meets his future cohort at the pier: Yngve, Lukas, Miller, Emma, Thom, and Cole. They boat to the peninsula for a bonfire. Someone pops champagne. Lukas lifts his cup and says, "This is it. . . . Our life. It starts now" (327). They chant, "To life" (327), their voices ringing through the night.