Born in San Francisco, California, Simpson is best known for his work in the films of John Ford and, in particular, for his portrayal of Pa Joad in The Grapes of Wrath in 1940. Simpson reportedly prospected for gold in Alaska in his youth, but by 1909 had gone into the theatre. He appeared in at least two plays on Broadway between 1909 and 1912, and made his motion picture debut in Cecil B. DeMille"s 1914 original film version of The Virginian in a bit part.
By 1923, when the film was remade, Simpson had progressed to playing the lead villain.
He worked up to 1959, the year of his death. His final film was The Horse Soldiers, his tenth film for Ford.
He died in Woodland Hills, California.