Raised in Avalon, Mississippi, John Hurt taught himself to play the guitar around the age of nine. He worked as a sharecropper and began playing at dances and parties, singing to a melodious fingerpicked accompaniment. His first recordings, were made for Okeh Records in 1928.

Hurt's recordings of "Frankie" and "Spike Driver Blues" were included in The Anthology of American Folk Music in 1952 which generated considerable interest in trying to locate him. John had recorded a song titled "Avalon Blues" which had a line that said, “Avalon my hometown, always on my mind”. In 1963, musicologist Dick Spottswood located Avalon on a turn-of-the-century map of Mississippi. He asked blues enthusiast Tom Hoskins, who was traveling that way, to enquire about Hurt. When Hoskins arrived in Avalon the first person he asked directed him to John Hurt's cabin.

Tom Hoskins persuaded an apprehensive Hurt, who original thought Hoskin’s was a government revenue officer, to perform several songs for him. Seeing that Hurt's guitar playing skills were still intact, encouraged him to move to Washington, D.C., and perform for a broader audience. His performance at the 1963 Newport Folk Festival caused his star to rise in the folk revival occurring at that time. He performed extensively at colleges, concert halls, and coffeehouses and appeared on The Tonight Show Starring Johnny Carson. He recorded albums for Vanguard, Piedmont, Rounder and Adelphi Records. Much of his repertoire was also recorded for the Library of Congress.

Hurt's influence spanned several music genres, including blues, spirituals, country, bluegrass and folk. A soft-spoken man, his nature was reflected in the work, which consisted of a mellow mix of country, blues, and old-time music.

Mississippi John Hurt died on November 2, 1966, of a heart attack, in the hospital at Grenada, Mississippi.