His distinctive single-string slide guitar style, songwriting and bottleneck technique influenced other Chicago blues guitarists such as Big Bill Broonzy, Robert Nighthawk, Muddy Waters, and Elmore James.

[4] His parents, John and Elizabeth Woodbridge, died when he was a child, and he moved to Tampa, Florida, where he was raised by his aunt and grandmother and adopted their surname, Whittaker.

Red also picked up some knowledge from early recordings of female blues singers like Ma Rainey, Bessie Smith, and Ida Cox.

'"[2] By 1925, having already perfected his slide technique, he had moved to Chicago, Illinois, and began his career as a street musician, adopting the name "Tampa Red", with reference to his childhood home and his light-colored skin.

Dorsey was an accomplished pianist, composer, and arranger who had performed and recorded with the leading female blues singers of the era, in particular Ma Rainey.

This allowed him to develop his trademark bottleneck style, playing single-string runs instead of block chords, which was a precursor of later blues and rock guitar soloing.

[8] Red's partnership with Dorsey ended in 1932, but he remained much in demand as a session musician, working with John Lee "Sonny Boy" Williamson, Memphis Minnie, Big Maceo, and many others.

He formed the Chicago Five,[9] a group of session musicians who created what became known as the Bluebird sound, a precursor of the small-group style of later jump blues and rock and roll bands.

[11] When blues expert Jim O'Neal discovered him on Chicago's South Side in 1974, he was living with his female companion, 81-year-old Effie Tolbert.

Red lived out his final years in Central Nursing Home, where he died from a heart attack while eating breakfast on the morning of March 19, 1981.

[14] Most of his singles were released before Billboard magazine began tracking blues (and other "race music") in October 1942, and accurate sales records are not available.

He also played as a sideman on recordings by Big Maceo Merriweather, John Lee "Sonny Boy" Williamson, Memphis Minnie, Ma Rainey, and Victoria Spivey.