The novel 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 to conceive, they consult a medical specialist, who, after repeated tests, informs Oliver that Jenny is ill and will soon die.
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. Instead of telling his father what the money is truly for, Oliver misleads him.