Townsend arrived in St. Louis when he was around ten years old, just before the '20s began. By the end of the '20s, he had landed a record contract with Columbia, cutting several sides of open-tuning slide guitar for the label. Two years later, he made some similar recordings for Paramount. During this time, Townsend began playing the piano, learning the instrument by playing along with Roosevelt Sykes records. Within a few years, he was able to perform concerts with pianists like Walter Davis and Henry Brown.

During the '30s, Townsend was a popular session musician, performing with many of the era's most popular artists. By the late '30s, he had cut several tracks for Bluebird. Those were among the last recordings he ever made as a leader. During the '40s and '50s, Townsend continued to perform and record as a session musician, but he never made any solo records.

In 1960, he led a few sessions, but they didn't receive much attention. Toward the end of the '60s, Townsend became a staple on the blues and folk festivals in America, which led to a comeback. He cut a number of albums for Adelphi and he played shows throughout America. By the end of the '70s, he had switched from Adelphi to Nighthawk Records.

Townsend had become an elder statesmen of St. Louis blues by the early '80s, recording albums for Wolf and Swingmaster and playing a handful of shows every year. That's the Way I Do It, a documentary about Townsend, appeared on public television in 1984. During the late '80s, Townsend was nearly retired, but he continued to play the occasional concert until his death in 2006.