Keith Carradine was born in San Mateo, California. He is the son of actress and artist Sonia Sorel (née Henius) and actor John Carradine. His paternal half-brothers are Bruce Carradine and the late David Carradine. His maternal half-brother is Michael Bowen, and his full brothers are Christopher and Robert Carradine.
Carradine's childhood was difficult. He said that his father drank and his mother “was a manic depressive paranoid schizophrenic catatonic — she had it all.” His parents were divorced in 1957, when he was eight years old. A bitter custody battle led to his father gaining custody of him and his brothers, Christopher and Robert, after the children had spent three months in a home for abused children as wards of the court. Keith said of the experience, "It was like being in jail. There were bars on the windows, and we were only allowed to see our parents through glass doors. It was very sad. We would stand there on either side of the glass door crying". He was raised primarily by his maternal grandmother, and he rarely saw either of his parents. His mother was not permitted to see him for eight years following the custody settlement.
After high school, Carradine entertained the thought of becoming a forest ranger, but opted to study drama at Colorado State University. He dropped out after one semester and drifted back to California moving in with his older half-brother, David. David encouraged Keith to pursue an acting career, paid for his acting and vocal lessons, and helped him get an agent.
Carradine's first notable film appearance was in director Robert Altman's McCabe & Mrs. Miller, in 1971. He went on to play one of the principal characters, a callow, womanizing folk singer, Tom Frank, in Altman's critically acclaimed 1975 movie, Nashville (See "Music and song writing"). He had difficulty shaking the image of Tom Frank following the popularity of the film. He felt the role gave him the reputation that he was "a cad".
In 1977, Carradine starred opposite Harvey Keitel in Ridley Scott's The Duellists. He has also acted in several offbeat films of Altman's protégé Alan Rudolph, playing a disarmingly candid madman in Choose Me (1984), an incompetent petty criminal in Trouble in Mind (1985), and an American artist in 1930s Paris in The Moderns (1988).
Other works include Emperor of the North Pole (1973), Pretty Baby (1978). He also appeared with his brothers David and Robert as the Younger brothers in Walter Hill's 1980 film, The Long Riders. Keith played Jim Younger in that film. In 1981, he appeared again under Hill's direction in Southern Comfort. In 1994, he had a cameo role as Will Rogers in Rudolph's 1994 film about Dorothy Parker, Mrs. Parker and the Vicious Circle. He co-starred with Daryl Hannah as homicidal sociopath John Netherwood in the 1995 thriller The Tie That Binds.