Chief Bromden, the half-Indian narrator of One Flew Over the Cuckoo’s Nest, has been a patient in an Oregon psychiatric hospital for ten years. His paranoia is evident from the first lines of the book, and he suffers from hallucinations and delusions. Bromden’s worldview is dominated by his fear of what he calls the Combine, a huge conglomeration that controls society and forces people into conformity. Bromden pretends to be deaf and dumb and tries to go unnoticed, even though he is six feet seven inches tall.

The mental patients, all male, are divided into Acutes, who can be cured, and Chronics, who cannot be cured. They are ruled by Nurse Ratched, a former army nurse who runs the ward with harsh, mechanical precision. During daily Group Meetings, she encourages the Acutes to attack each other in their most vulnerable places, shaming them into submission. If a patient rebels, he is sent to receive electroshock treatments and sometimes a lobotomy, even though both practices have fallen out of favor with the -medical community.

When Randle McMurphy arrives as a transfer from the Pendleton Work Farm, Bromden senses that something is different about him. McMurphy swaggers into the ward and introduces himself as a gambling man with a zest for women and cards. After McMurphy experiences his first Group Meeting, he tells the patients that Nurse Ratched is a ball-cutter. The other patients tell him that there is no defying her, because in their eyes she is an all-powerful force. McMurphy makes a bet that he can make Ratched lose her temper within a week.

At first, the confrontations between Ratched and McMurphy provide entertainment for the other patients. McMurphy’s insubordination, however, soon stimulates the rest of them into rebellion. The success of his bet hinges on a failed vote to change the television schedule to show the World Series, which is on during the time allotted for cleaning chores. McMurphy stages a protest by sitting in front of the blank television instead of doing his work, and one by one the other patients join him. Nurse Ratched loses control and screams at them. Bromden observes that an outsider would think all of them were crazy, including the nurse.

In Part II, McMurphy, flush with victory, taunts Nurse Ratched and the staff with abandon. Everyone expects him to get sent to the Disturbed ward, but Nurse Ratched keeps him in the regular ward, thinking the patients will soon see that he is just as cowardly as everyone else. McMurphy eventually learns that involuntarily committed patients are stuck in the hospital until the staff decides they are cured. When McMurphy realizes that he is at Nurse Ratched’s mercy, he begins to submit to her authority. By this time, however, he has unintentionally become the leader for the other patients, and they are confused when he stops standing up for them. Cheswick, dismayed when McMurphy fails to join him in a stand against Nurse Ratched, drowns in the pool in a possible suicide.

Cheswick’s death signals to McMurphy that he has unwittingly taken on the responsibility of rehabilitating the other patients. He also witnesses the harsh reality of electroshock therapy and becomes genuinely frightened by the power wielded by the staff. The weight of his obligation to the other patients and his fear for his own life begins to wear down his strength and his sanity. Nevertheless, in Part III, McMurphy arranges a fishing trip for himself and ten other patients. He shows them how to defuse the hostility of the outside world and enables them to feel powerful and masculine as they catch large fish without his help. He also arranges for Billy Bibbit to lose his virginity later in the novel, by making a date between Billy and Candy Starr, a prostitute from Portland.

Back on the ward in Part IV, McMurphy reignites the rebellion by getting into a fistfight with the aides to defend George Sorenson. Bromden joins in, and they are both sent to the Disturbed ward for electroshock therapy. McMurphy acts as if the shock treatments do not affect him, and his heroic reputation grows. Nurse Ratched brings him back to the ward so the other patients can see his weakened state. The patients urge McMurphy to escape, but he has arranged Billy’s date for that night, and he refuses to let Billy down. McMurphy bribes Mr. Turkle, the night aide, to sneak Candy into the hospital, and they have a party on the ward. Billy has sex with Candy while McMurphy and the other patients smoke marijuana and drink. Harding tries to get McMurphy to escape with Candy and Sandy to Mexico, but McMurphy is too wasted and falls asleep.

The aides discover the mess the next morning, setting off a series of violent events. When Nurse Ratched finds Billy with Candy, she threatens to tell Billy’s mother. Billy becomes hysterical and commits suicide by cutting his throat. McMurphy attacks Ratched, ripping open the front of her dress and attempting to strangle her. In retaliation, she has him lobotomized, and he returns to the ward as a vegetable. However, Ratched has lost her tyrannical power over the ward. The patients transfer to other wards or check themselves out of the hospital. Bromden suffocates McMurphy in his bed, enabling him to die with some dignity rather than live as a symbol of Ratched’s power. Bromden, having recovered the immense strength that he had believed lost during his time in the mental ward, escapes from the hospital by breaking through a window.