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After 1934, Horne joined Noble Sissle’s Orchestra. She toured with them and it was during this time she made her first records, which were issued by Decca. It was after she separated from her first husband, she deiced to tour with bandleader Charlie Barret from 1940 to 1941. She left in 1941 because she disliked the travel. She left the band and decided to work at the Café Society in New York. She was a featured vocalist on NBC’s popular jazz series “The Chamber Music Society of Lower Basin Street”, after replacing Dinah Shore. The show’s resident maestros, Henry Levine and Paul Laval, recorded with Horne in June 1941 for RCA Victor. Horne decided to leave the show after only 6 months when she was hired by former Café Trocadera manager Felix young to perform in a Cotton Club -stye revue in the Sunset Strip in Hollywood. It was a gig she couldn’t turn down.

By the mid-1950s, Horne was losing interest with Hollywood and decided to focus more on her nightclub career. She made only two major appearances for the studio during the 1950s. These productions were Duchess of Idaho and the 1956 musical  Meet Me in Las Vegas.  Horne states that the reason she left hollywood was becasue she was “tired of being typecast as a Negro who stands against a pillar singing a song’. After leaving Hollywood, Horne decided to establish herself as one of the premier nightclub performers of the post-war era. During this time she headlined at clubs and hotels throughout the U.S., Canada, and Europe, including the Sands Hotel in Las Vegas, the Cocoanut Grove in Los Angeles, and the Waldorf-Astoria in New York. From the late 1950s through to the 1960s, Horne was a staple of TV variety shows, appearing multiple times on Perry Como’s  Kraft Music Hall, The Ed Sullivan Show, The Dean Martin Show and The Bell Telephone Hour