While retaining many of the novel's themes and motifs, the filmed version of One Flew Over the Cuckoo's Nest differs in several significant ways. The film, released in 1975, won Academy Awards for Best Picture, Best Actor (Jack Nicholson), Best Actress (Louise Fletcher), Best Screenplay Adapted from Other Material (Lawrence Hauben and Bo Goldman), and Best Director (Milos Forman). Since its release, the film has been certified as one of the Top 100 American Films by the American Film Institute.

The most notable difference between the film and the novel is the story's point of view. In the novel, Chief Bromden is the narrator who reveals the story of the battle of wills between Nurse Ratched and Randle Patrick McMurphy. In fact, Chief arguably is the novel's hero who undergoes the most notable changes in the novel. While detailing the events in the mental institution, Chief reveals biographical information of his own life before his institutionalization. We learn that Chief is a paranoid schizophrenic, a war veteran, and a half-breed Indian whose white mother conspired with the U.S. government to emasculate his proud father, an American Indian whose name Tee Ah Millatoona translates as "Pine-That-Stands-Tallest-on-the-Mountain."

The filmed version discards Chief as the story's narrator, discards the background story of Chief, and relegates his character to a secondary — albeit important — character to McMurphy. In the film, McMurphy is clearly the hero.