Kesey relates the story of the clash between the repressive and rebellious wills, respectively, of Nurse Ratched and Randle Patrick McMurphy from the viewpoint of a paranoid schizophrenic named Chief Bromden. With the exception of a fishing excursion led by McMurphy with an accompanying doctor and eleven patients, the entire novel is set in the psychiatric hospital where McMurphy may or may not be feigning insanity to escape the hard labor of a work farm. The patients are classified either as Acutes or Chronics; the former considered curable and whose stay at the hospital is voluntary; while the latter are failed attempts of the hospital's staff to force its conformity on patients through electroshock therapy and lobotomies. The Acutes have succumbed to incomplete lives wherein the arbitrary whims of an increasingly mechanized and feminized society has emasculated them and rendered them ineffectual.
McMurphy invigorates the Acutes and the Chronic Chief with his open, frank heterosexuality, anti-academic, and rebellious approach to life. This contrasts strongly with Nurse Ratched's attempts to control the men, inevitably leading to a series of comically rendered showdowns. The novel turns more serious, however, when the men begin to adopt McMurphy's attitudes, resulting in Nurse Ratched's escalation of her repressive tactics. Increasingly relying on New Testament portrayals of the Passion and crucifixion of Jesus Christ, Chief relates Ratched's victory over McMurphy when she has him lobotomized. Her victory is short-lived, however, as McMurphy's lessons to the men result in many of the Acutes leaving the hospital. Chief suffocates McMurphy and escapes from the hospital, in an ending that is both heroic and ambiguous.