"Chief" Bromden, a schizophrenic Native American man who pretends to be deaf and dumb so that everybody ignores him, narrates One Flew Over the Cuckoo’s Nest. The novel begins the morning that a new "Admission," Randle McMurphy, is introduced to an insane asylum where Chief is the longest-residing patient. McMurphy is larger than life, intelligent, and observant. He stirs up the ward immediately by introducing friendly competition – gambling – and encourages the men to rebel against the petty rules created and enforced by Nurse Ratched (often referred to as "Big Nurse").
McMurphy places a bet with the other men on the ward that he can break Nurse Ratched without: a) getting sent to the Disturbed Ward, b) getting treated with electroshock therapy, or c) being lobotomized. Slowly, McMurphy undermines Nurse Ratched’s system of control while remaining Mr. Nice Guy. She’s no fool, however. What McMurphy doesn’t understand is that Nurse Ratched has a lot of control over the situation. Since he’s a patient in the asylum, she can keep him locked up as long as she wants. As long as he’s under her rule, she has the power to send him for electroshock therapy or a lobotomy. The question is simply whether she’ll utilize her power against him or not. When McMurphy figures this out, he steps back and begins to behave – but not for long.
Just when Nurse Ratched thinks she has the upper hand, McMurphy steps back up to the plate and challenges her authority again. This time, though, he goes too far. He sneaks two prostitutes into the ward, gets everybody drunk, and also breaks into the prescription drug cabinet.
After the incident, Nurse Ratched guilt-trips all the men back into her control. Speaking of going too far, Nurse Ratched goes way, way too far. She threatens one of the patients, Billy Bibbit, by saying she’ll tell his mother about his visit with a "cheap" woman. Bibbit panics, which demoralizes the other inmates. Bibbit suddenly commits suicide after reflecting on the shame that Big Nurse is about to bring down on his head.
Of course, Nurse Ratched blames McMurphy for Bibbit’s death, which McMurphy doesn’t take so well. In fact, he’s so angry that he shatters the glass over the nurse’s station for a second time. Then, in one of the biggest scenes in the novel, McMurphy tears Nurse Ratched's shirt off and reveals her breasts. Why’s this move so important? Well, McMurphy has proved that the Big Nurse is "only" a woman: in the 1960s women were considered the "weaker sex" by men, and therefore less powerful than men on the ward. McMurphy also mangles Nurse Ratched physically, choking her badly.
The momentum of the crazy situation allows Nurse Ratched to send McMurphy upstairs for a lobotomy. When McMurphy returns to the ward, he’s a vegetable. Chief realizes he can’t let McMurphy suffer for years in the prison of his body. That night, he smothers McMurphy to death. Chief then escapes from the hospital after breaking a window. His getaway is only possible because of McMurphy, who previously had taught Chief how to lift a heavy panel in the tub-room and break the windows. Chief reaches the highway, where he catches a ride with a Mexican guy and heads to Canada and freedom.