The film tells of Oliver Barrett IV, who comes from a family of wealthy and well-respected Harvard University graduates. Partly to break the traditional Ivy League mold, the Harvard student meets and falls in love with Jennifer Cavelleri, a working-class, quick-witted Radcliffe College student. Upon graduation from college, the two decide to marry against the wishes of Oliver's father, who thereupon severs ties with his son.
Without his father's financial support, the couple struggles to pay Oliver's way through Harvard Law School with Jenny working as a private school teacher. Graduating third in his class, Oliver takes a position at a respectable New York law firm.
With Oliver's new income, the pair of 24-year-olds decide to have a child. After failing, they consult a medical specialist, who after repeated tests, informs Oliver that Jenny is ill and will soon die. Oliver then tries again. While this is not stated explicitly, she appears to have leukemia.
As instructed by his doctor, Oliver attempts to live a "normal life" without telling Jenny of her condition. Jenny nevertheless discovers her ailment after confronting her doctor about her recent illness. With their days together numbered, Jenny begins costly cancer therapy, and Oliver soon becomes unable to afford the multiplying hospital expenses. Desperate, he seeks financial relief from his father. When the senior Barrett asks if he needs the money because he got some girl "in trouble", Oliver says yes instead of telling his father the truth about Jenny's condition.
From her hospital bed, Jenny speaks with her father about funeral arrangements, then asks for Oliver. She tells him to avoid blaming himself, and asks him to embrace her tightly before she dies. They lie together on the hospital bed.
The novel also includes the double meaning of a love story between Oliver and his father, highlighted by the scene between Oliver and his father at the end of the book. When Mr. Barrett realizes that Jenny is ill and that his son borrowed the money for her, he immediately sets out for New York. By the time he reaches the hospital, Jenny is dead. Mr. Barrett apologizes to his son, who replies with something Jenny once told him: "Love means never having to say you're sorry."