By 1920 he had become an alcoholic and itinerant musician, based in Crystal Springs but travelling widely around the South, sometimes accompanied by Papa Charlie McCoy. In 1928 he made his first recordings with McCoy for Victor Records. The recordings included "Canned Heat Blues", in which he sang of drinking methanol from the cooking fuel Sterno. The song features the refrain "canned heat, mama, sure, Lord, killing me." The blues group Canned Heat took their name from this song. Johnson's "Big Road Blues" inspired Canned Heat's song, "On the Road Again". A significantly different version of the song appears as "Canned Heat" on the Big Road Blues album by K. C. Douglas.
He recorded two further sessions, in August 1928 and for Paramount Records in December 1929. He did not record again, mistakenly believing that he had signed away his right to record . This resulted on a legal settlement with The Mississippi Sheiks who had used Johnson's 'Big Road Blues' melody in their enormously successful "Sitting on Top of the World". Johnson was party to the copyright settlement, but was too drunk at the time to understand what he had signed to.
Johnson's recordings established him as the premier Delta blues vocalist of his day, with a powerful voice that could go from a growl to a falsetto. He was also an accomplished guitarist. His style influenced later blues singers such as Robert Nighthawk and Howlin' Wolf, whose song "I Asked for Water (She Brought Me Gasoline)" was based on Johnson's "Cool Water Blues". He was a talented composer, blending fragments of folk poetry and personalized lyrics into set guitar accompaniments to craft striking blues compositions such as "Maggie Campbell".
To enhance his fame, Johnson cultivated a sinister persona. According to his brother LeDell, he claimed to have sold his soul to the devil in exchange for his mastery of the guitar. This story was later also, and probably erroneously, associated with Robert Johnson, to whom he was unrelated. Tommy Johnson also played tricks with his guitar, playing it between his legs and behind his head, and throwing it in the air while playing.
Johnson remained a popular performer in the Jackson area through the 1930s and 1940s, sometimes performing with Ishman Bracey. He was highly influential on other performers, partly because he was willing to teach his style and his repertoire. Tommy Johnson's influence on local traditions is discussed by David Evans in 'Tommy Johnson' and 'Big Road Blues.
He died of a heart attack after playing a party in 1956. He is buried in the Warm Springs Methodist Church Cemetery outside of Crystal Springs, Mississippi. In 2001 a headstone was commissioned through the Mt. Zion Memorial Fund, a Mississippi non-profit corporation, by the family of Tommy Johnson and paid for by musician Bonnie Raitt. The large, granite memorial engraved with Johnson's portrait has not been placed on Johnson's grave, however, due to a bitter, ongoing dispute between Tommy Johnson's family, led by his niece, Vera Johnson Collins, the owners of farm property encircling the cemetery, and the Copiah County Board of Supervisors. The headstone has remained on public display in the Crystal Springs, Mississippi Public Library since being unveiled on October 20, 2001. An annual Tommy Johnson Blues Festival is now held in Crystal Springs, Mississippi, on every third weekend in October.
In the Adult Swim show Metalocalypse, the Tommy Johnson story is parodied when the metal band Dethklok is encouraged by blues man "Mashed Potato Johnson" to channel their depression into the Blues. He is described as having sold his soul to the devil in order to have a "standard bluesman rapsheet." Mashed Potato Johnson tells the band that every great blues singer has sold his soul to the devil and that this practice is essential to becoming a true blues musician.