The movie is told in flashback, narrated by Edmond O'Brien, who plays Gaddis, the author of the book upon which the movie is based.

Robert Stroud is imprisoned as a young man for committing a murder in Alaska. He is shown as a rebellious inmate, fighting against a rigid prison system. In an early scene he breaks open the window of a prison train, to allow the suffocating inmates to breathe.

He is sentenced to life in prison after stabbing a guard who denied him a visit from his mother (Thelma Ritter). The terms of the sentence require that he be kept in solitary confinement for the rest of his life. His rebellious attitude--portrayed in the film as justifiable--puts him in conflict with the warden of Leavenworth Prison (Karl Malden).

To break the monotony, Stroud adopts a bird as a pet. When the bird gets sick, he experiments with a cure. As the years pass, working with many birds, he becomes an expert on bird diseases. He publishes a book on bird remedies, and then writes a history of the U.S. penal system that is suppressed. He remains rebellious and at odds with authority. He marries and then divorces a woman who had corresponded with him about birds. This turns his mother against him.

Stroud is abruptly transferred to the federal penitentiary at Alcatraz, a new maximum security institution where he is not permitted to keep birds. He is now growing elderly, and though still rebellious he is a positive influence, and helps stop a prison rebellion in 1946. He is transfered to another prision in Missori after a petition campaign sometime in the 1950s, but is yearly denied parole. The film ends as he is being driven off after having met a reporter who tried to help him with a release.

Burt Lancaster's portrayal of Stroud stirred sympathy with the general public. However, prison historians have pointed out that the real Stroud was a merciless killer who showed no remorse for his crimes. Yet this was the demonstrated opinion of the prison officials in the film too. It was in the context of this that their rigid thinking about his being kept in solitary confinement, and never being released was justified.

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