In 1953 Ike Turner recruited Milton for the legendary Sun Records. His Sun singles didn't achieve success, and he spent subsequent years hopping from label to label until he started a label, Bobbin, with a St. Louis DJ. When they had a falling out, Little Milton moved to the Chess subsidiary Checker (which had been distributing Bobbin), even bringing at least one track recorded for Bobbin. Soon Milton branched out from performing to producing and managing other performers, and also gained his first hit (on the R&B chart) in 1962, "Mean to Me."
This period of Little Milton's career is well covered on the 16-song Chess CD Greatest Hits in the label's 50th Anniversary Collection series.