Hill was born in New Orleans, Louisiana, United States. By his teens he was playing drums in local bands, and in 1951 he formed his own group, the House Rockers. After periods performing as drummer with Professor Longhair and then Huey “Piano” Smith, Hill formed a new version of the House Rockers in 1958, which enabled him to focus on singing with the band.

Upon its 1960 release on Minit Records, “Ooh Poo Pah Doo” emerged as a favorite at Mardi Gras, selling 800,000 copies and reaching #3 on the Billboard R&B chart and #28 in the Billboard Hot 100 pop chart. There have been over 100 cover versions of “Ooh Poo Pah Doo” recorded and performed live over the years by other popular musicians.

His follow-up “Whip It On Me” reached #91 on the Billboard Hot 100 in 1960. Further recordings in New Orleans were less successful, and he moved to California to work with fellow New Orleans musicians including Harold Battiste and Mac Rebennack. In this period, he wrote songs recorded by Ike and Tina Turner, Sonny and Cher, and Willie Nelson.

A 1972 solo album was unsuccessful, and he began to suffer financial difficulties exacerbated by a drinking problem. These problems continued after his return to New Orleans in 1977, and several benefit gigs did little to revive his personal or professional fortunes.

Hill died of heart and renal failure in New Orleans in September 1996, at the age of 63. He is buried in Holt Cemetery in New Orleans, in a pauper’s grave for the poorest citizens of the city.

Two of his grandsons are James and Troy “Trombone Shorty” Andrews. The pair performed “Ooh Poo Pah Doo” in Episode 7 of the HBO series Treme. A third grandson, Travis “Trumpet Black” Hill, was a rising New Orleans-based performer. Trumpet Black died from an infection while on tour in Tokyo on May 4, 2015.

On June 25, 2019, The New York Times Magazine listed Jessie Hill among hundreds of artists whose material was reportedly destroyed in the 2008 Universal fire.