Keith Carradine was born in San Mateo, California. He is the son of actress and artist Sonia Sorel (nee Henius), and actor John Carradine. His paternal half-brothers are Bruce and David Carradine, his maternal half-brother is Michael Bowen, and his full brothers are Christopher and Robert Carradine. His maternal great-grandfather was biochemist Max Henius, and his maternal great-grandmother was the sister of historian Johan Ludvig Heiberg.

Carradine's first notable film appearance was in director Robert Altman's McCabe & Mrs. Miller (1971). His next film, Emperor of the North Pole (1973), was re-released with a shorter title Emperor of the North. Carradine played a young aspiring hobo. The film was directed by Robert Aldrich and also starred Lee Marvin and Ernest Borgnine. Carradine then starred in Altman's film Thieves Like Us (1974), then played a principal character, a callow, womanizing folk singer, Tom Frank, in Altman's critically acclaimed film Nashville (1975; 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 of being "a cad."  In 1977, Carradine starred opposite Harvey Keitel in Ridley Scott's The Duellists. Pretty Baby followed in 1978. He has acted in several offbeat films of Altman's protege 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).  He appeared with brothers David and Robert as the Younger brothers in Walter Hill's film The Long Riders (1980). 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 film about Dorothy Parker, Mrs. Parker and the Vicious Circle. He co-starred with Daryl Hannah as homicidal sociopath John Netherwood in the thriller The Tie That Binds (1995). In 2011, he starred in Cowboys and Aliens, an American science fiction western film directed by Jon Favreau also starring Daniel Craig, Harrison Ford, and Olivia Wilde. Carradine traveled to Tuscany in 2012 to executive produce and star in John Charles Jopson's Edgar Allan Poe inspired film 'Terroir'. In 2013, he starred in Ain't Them Bodies Saints, which won the 2013 Sundance Film Festival award for cinematography. In 2016 Keith played Edward Dickinson father of Emily Dickinson in A Quiet Passion the biographical film directed and written by Terence Davies about the life of the American poet.  In 2016 Carradine returned to star in his fourth Alan Rudolph film Ray Meets Helen alongside actress Sondra Locke.

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