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Never Let Me Go takes place in a dystopian version of late 1990s England, where the lives of ordinary citizens are prolonged through a state-sanctioned program of human cloning. The clones, referred to as students, grow up in special institutions away from the outside world. As young adults, they begin to donate their vital organs. All “donors” receive care from designated “carers,” clones who have not yet begun the donation process. The clones continue to donate organs until they “complete,” which is a euphemism for death after the donation of three or four organs. However, this premise is not immediately apparent to the reader. At the start of the novel, narrator Kathy H. merely introduces herself as a thirty-one-year-old carer. She has been a carer for nearly twelve years, but will leave her role in a few months. Kathy explains that she wants to revisit her memories of Tommy and Ruth, two friends who grew up with her at the Hailsham school. Kathy does not explain the donation program, or mention that Hailsham students are clones.
Although Kathy’s narration is often nonlinear, the novel’s three parts roughly align with three stages in her life. In Part One, Kathy remembers her childhood at Hailsham. She describes her friendship with Ruth, whose temperamental personality contrasts with her own quiet demeanor. At Hailsham, Ruth often annoys Kathy by pretending to have special knowledge and privileges. Kathy also describes Tommy, a student known for throwing violent temper tantrums. Tommy is initially an outcast among his peers because he lacks artistic ability, which the Hailsham staff (part teacher, part parent figures known as “guardians”), and its students value highly. Kathy sympathizes with Tommy, and tries to calm him down during one of his tantrums. Tommy later learns to control his temper after a guardian named Miss Lucy assures him that it is not necessary for him to be creative.
Although the students learn vaguely about the donation program, their guardians shield them from a full understanding of their future. Miss Lucy disagrees with this indirect approach, and often exhibits strange behavior in front of the students as a result, in one instance telling them explicitly about their futures. After Miss Lucy speaks with Tommy about his artwork, he and Kathy theorize that creativity may be connected to donations. They speculate about Madame, a woman who visits Hailsham to collect the best student artwork. Madame is rumored to keep this art in a personal gallery. Kathy later encounters Madame in the girls’ dormitory, while Kathy dances to the song “Never Let Me Go.” The song is Kathy’s favorite track on Songs After Dark, a Judy Bridgewater album that is one of her most prized possessions. When the song ends, Kathy sees Madame crying in the doorway. Shortly afterwards, Kathy loses her tape. Tommy’s temper returns during their last summer at Hailsham. Kathy thinks he is upset about his recent breakup with Ruth, whom he has dated for six months. But Tommy is upset about Miss Lucy, who recently told him that she was wrong to dismiss the importance of creativity. Miss Lucy departs Hailsham abruptly, and Tommy mends his relationship with Ruth.
In Part Two, Kathy moves with Ruth and Tommy to a transitional housing facility known as the Cottages. They adjust to their new lives, becoming acquainted with the “veteran” students living there already. Ruth often ignores Tommy and Kathy in her efforts to blend in with the veterans, who are not from Hailsham. Kathy notices that the veterans regard the Hailsham students with awe. One couple, Chrissie and Rodney, are especially interested in Hailsham. They convince Ruth to go with them to Norfolk, where Rodney claims to have seen Ruth’s “possible” in an open-plan office (a “possible” is a human that resembles a specific clone and from whom that clone's DNA may have been copied). Kathy is skeptical of Rodney’s story, especially since it features Ruth’s “dream future” of working in an open-plan office. In the end, Kathy, Tommy, Ruth, Rodney, and Chrissie all drive to Norfolk.
In Norfolk, Chrissie and Rodney ask about a rumored exception allowing Hailsham couples in love to defer their donations. Ruth pretends to know something about deferrals, which surprises Kathy and Tommy. The students eventually find the open-plan office. Rodney points to a woman in the window, and they all agree that she could be Ruth’s legitimate possible. They follow her to an art gallery, where they realize that the woman does not actually resemble Ruth. In her disappointment, Ruth says that the students are modeled only on “trash.” Ruth goes off with Chrissie and Rodney. Meanwhile, Tommy and Kathy find a copy of Kathy’s lost tape in a secondhand store. Tommy tells Kathy that he has begun drawing pictures of imaginary animals. He thinks Madame uses the students’ artwork to determine if couples applying for deferrals are truly in love. After Norfolk, Ruth stops talking about her dream future. Tommy shows his drawings to Kathy, who finds them puzzling but captivating. Meanwhile, Kathy’s friendship with Ruth grows increasingly tense. Ruth reveals that she knows Kathy likes Tommy, but says that Tommy will never return Kathy’s feelings. Shortly afterwards, Kathy submits her application for carer training and departs.
Part Three focuses on Kathy’s time as carer. While Kathy is good at her job, the work is both difficult and lonely. She unexpectedly runs into a Hailsham friend named Laura, who is also a carer. They talk about Ruth, who had a bad first donation. They also talk about Hailsham, which has closed. Kathy becomes Ruth’s carer, but their relationship is strained and guarded. One day, Ruth expresses a desire to visit a beached fishing boat near Tommy’s recovery center. They pick up Tommy on the way to the boat, which they find bleached and crumbling in a marsh. The marsh reminds both Tommy and Ruth of Hailsham. They also discuss Chrissie, who completed on her second donation. On the return trip, Ruth apologizes for keeping Tommy and Kathy apart. She encourages them to pursue a deferral, revealing that she has discovered Madame’s home address. In the weeks that follow, Kathy and Ruth reminisce peacefully about Hailsham and the Cottages. Ruth also encourages Kathy to become Tommy’s carer.
Ruth completes after her second donation. Tommy gives his third donation, and Kathy becomes his carer. They spend their days reading and talking at his recovery center. Eventually, they also begin to have sex. Hoping to pursue a deferral, they go to visit Madame at the address Ruth provided. Madame invites them inside and listens to their request, after which Miss Emily appears from the next room. Miss Emily says that deferrals do not exist. She explains that Hailsham was part of a progressive movement committed to raising clones more humanely. Madame used to exhibit the students’ artwork to show the outside world that clones had souls. Although the movement once had many supporters, changing public opinion eventually forced Hailsham to close. On the drive back to his recovery center, Tommy asks Kathy to pull over. He walks into the woods and begins screaming. Kathy goes to Tommy and holds him. Soon after, Tommy gives his fourth donation and completes. Kathy drives to a field in Norfolk, where she allows herself to imagine Tommy on the horizon. Then she drives away.