Born in Baltimore, Maryland, the son of Alexander and Mary. He studied at Dickinson College, Carlisle, Pennsylvania and received an international law degree in 1911. Muse was acting in New York by the 1920s, during the Harlem Renaissance with two Harlem theatres, Lincoln Players and Lafayette Players. Muse moved to Chicago for a while, and then moved to Hollywood and performed in Hearts in Dixie (1929), the first all-black movie. For the next fifty years, he worked regularly in minor and major roles. Muse appeared as an opera singer, minstrel show performer, vaudeville and Broadway actor; he also wrote songs, plays, and sketches.
He was the major star in Broken Earth (1936), related the story of a black sharecropper whose son miraculously recovers from fever through the father's fervent prayer. Shot on a farm in the South with nonprofessional actors (except for Clarence Muse), the film's early scenes focused in a highly realistic manner on the incredible hardship of black farmers, with plowing scenes. Muse and Langston Hughes wrote the script for Way Down South (1939). The film was notable for its casting of African American actors in central roles, and for tackling racial issues in the South. Muse also performed in Broken Strings (1940), as a concert violinist who opposes the desire of his son to play "swing". In 1955-1956, Muse was a regular on the weekly TV version of Casablanca, playing Sam the pianist, and in 1959, he appeared in the film Porgy and Bess, with Sidney Poitier, Dorothy Dandridge and Sammy Davis Jr. Other film credits include Buck and the Preacher (1972), and Car Wash (1976), as "Snapper". His last acting role was in The Black Stallion (1979), with Mickey Rooney and Teri Garr.
He received an honorary doctor of humanities degree from Bishop College, Dallas, Texas, in 1972, and was a member of Phi Beta Sigma Fraternity, Inc., Omega Chapter. Clarence Muse died in Perris Valley, California, October 13, 1979.