Originally performing in minstrel and medicine shows, Jackson was playing all around Chicago in the early 1920s, soon recording "Papa's Lawdy Lawdy Blues" and "Airy Man Blues", the first recordings by a male singer of the blues. One of his following tracks, "Salty Dog Blues", became perhaps his most famous song. He soon began cutting records with Ida Cox, Hattie McDaniel and Ma Rainey.
The late 1920s saw Jackson reach the pinnacle of his career, recording "Papa Charlie and Blind Blake Talk About It" (a two-part song) with Blind Blake. A few more recordings followed before the 1930s, but then Jackson left Paramount Records and moved to Okeh, recording with Big Bill Broonzy.