Fontella Bass was born in St. Louis, Missouri, the daughter of gospel singer Martha Bass (a member of the Clara Ward Singers). At an early age, Fontella showed great musical talent – at five years old she was providing the piano accompaniment for her grandmother's singing at funeral services, she was singing in her church's choir at six years old and by the time she was nine she was accompanying her mother on tours throughout the American South and Southwest.
Fontella continued touring with her mother until the age of sixteen. As a teenager, Bass was attracted by more secular music. She began singing R&B songs at local contests and fairs while attending Soldan High School where she graduated from in 1958. At seventeen, she started her professional career working at the Showboat Club near Chain of Rocks, Missouri. In 1961, she auditioned on a dare for the Leon Claxton carnival show and was hired to play piano and sing in the chorus for two weeks, making $175 per week for the two weeks it was in town. She wanted to go on tour with Claxton but her mother refused and according to Bass "... she literally dragged me off the train". It was during this brief stint with Claxton that she was heard by vocalist Little Milton and his bandleader Oliver Sain who hired her to back Little Milton on piano for concerts and recording.
Bass originally only played piano with the band, but one night Milton didn't show up on time so Sain asked her to sing and she was soon given her own featured vocal spot in the show. Milton and Sain eventually split up and Bass went with Sain; he also recruited male singer Bobby McClure and the group became known as "The Oliver Sain Soul Revue featuring Fontella and Bobby McClure".
With the support of Bob Lyons, the manager of St. Louis station KATZ, Bass recorded several songs released through Bobbin Records and produced by Ike Turner. She saw no notable success outside her home town. It was also during this period she met and subsequently married the noted jazz trumpeter Lester Bowie.