Missouri-born Jane Darwell was born Patti Woodard, the daughter of William Robert Woodard, president of the Louisville Southern Railroad, and Ellen (Booth) Woodard, in Palmyra, Missouri, where she grew up on a ranch . She nursed ambitions to be an opera singer, but put it off because of her father's disapproval (she eventually changed her name to Darwell from the family name of Woodard so as not to "sully" the family name). Making her stage debut at age 33, she was almost 40 when she made her first film, a silent, in 1913.

She easily made the transition from silents to talkies, and specialized in playing kindly, grandmotherly types. Her most famous role was as Ma Joad, the glue that held the Joad family together, in the classic The Grapes of Wrath (1940), for which she won the Academy Award. She was, however, memorably cast against type in The Ox-Bow Incident (1942), as the shrewish, cackling Ma Grier, a lynch mob leader, and again in Caged (1950), as the unsympathetic prison matron in charge of the isolation ward.

She made over 200 films. Her last, Mary Poppins (1964), was made at the express request of Walt Disney; she had retired and was living at the Motion Picture Country Home and Disney came out personally to ask her to appear in the film, after which she went back into retirement. She died in 1967 after suffering a stroke and a heart attack, and was interred at Forest Lawn Memorial Park in Glendale, California.