Patton befriended House, who began working as a musician around the Kirby Plantation. In 1930, Patton brought him, guitarist Willie Brown, and pianist Louise Johnson to Grafton, Wisconsin, for a recording session with Paramount Records. House's influence on the Delta School of musicians can be judged from a handful of recordings made in Grafton. His song "Preachin' The Blues Part I & II" was a six-minute biography of his life and served as inspiration for Robert Johnson 's "Preaching Blues" and "Walking Blues." House's powerful vocals and slashing slide guitar style established him as a giant of the Delta School but did not lead to commercial success. House continued playing with Willie Brown during the 1930s and developed a relationship with a young Robert Johnson after moving to Robinsonville, Mississippi. After Johnson had learned to play guitar, he began to gig with House and Brown, learning the older musicians' licks.

House, Willie Brown, Fiddlin' Joe Martin, and Leroy Williams were recorded by folklorist Alan Lomax near Lake Cormorant, Mississippi, in 1941 for the Library of Congress. Lomax returned the next year to record House in Robinsonville, but the musician did not make another commercial record until the "blues revival" of the 1960s. His influence, however, would be felt through the recordings of Johnson, Muddy Waters , Howlin' Wolf , Elmore James , Robert Nighthawk , and other successful blues artists.

Son House died October 19, 1988.