After playing in Swing orchestras he founded his own band in 1945. This band played with Wynonie Harris and Charles Brown. In 1947 he and Bardu Ali opened the Barrelhouse Club in the Watts district of Los Angeles. He reduced the size of his band and hired singers Mel Walker, Little Esther and the Robins (who later became the Coasters). With this band, which toured extensively throughout the United States as the California Rhythm and Blues Caravan, he had a long string of rhythm and blues hits through 1952.
In the late 1940s he discovered Big Jay McNeely, who then performed on his "Barrelhouse Stomp." In the 1950s he discovered Etta James, for whom he produced her first hit, "Roll With Me, Henry," (also known as "The Wallflower"). As an artist and repertory man for King Records he also discovered Jackie Wilson, Hank Ballard, and Little Willie John, among others. He also became an influential disk jockey in Los Angeles. However, he continued to perform, and in 1958 he had a hit with his best-known recording "Willie and the Hand Jive."
In the 1960s he entered journalism and politics, losing a campaign for a seat in the California Assembly (one reason for the loss may be that he ran under his much less well known real name). He then became chief of staff for Democratic Congressman Mervin Dymally.
He continued performing into the 1980s, although because of his many other interests he went through long periods where he did not perform.
He was elected to the Rock and Roll Hall of Fame in 1994.
He is the father of Shuggie Otis.