He began his musical career as a teenager. He sang and was self-educated on guitar and drums. He was in a band that played in speakeasies in Terre Haute. During the 1930s, he formed a band, spent eight years living in Akron, Ohio, and performed five days a week on a radio show in Dayton, Ohio. The station manager thought he needed a catchier name, so Crothers suggested "Scatman" for his scat singing. He married Helen, a native of Steubenville, Ohio, in 1937. In the 1940s, the couple moved to California.
He performed in Los Angeles, Las Vegas, and at the Apollo Theater in Harlem, New York City. Capitol released several of his singles: "I'd Rather Be a Hummingbird", "Blue-eyed Sally", and "Television Blues". High Fidelity Records released his album Rock and Roll with Scatman Crothers. He went on USO tours with Bob Hope. Crothers also performed with bandleader Slim Gaillard. According to the jacket notes of the Let Freedom Sing CD set, Crothers was part of the music group The Ramparts, who sang "The Death of Emmett Till" (1955), a song by A. C. Bilbrew.