Sonny Boy Williamson 1, he was born near Jackson, Tennessee in 1914. His original harmonica recordings were considered to be in the country blues style, but he soon demonstrated skill at making harmonica a lead instrument for the blues, and popularized the instrument for the first time in a more urban blues setting. He has been called "the father of modern blues harp".

His very first recording, "Good Morning, School Girl", was a major hit on the 'race records' market in 1937. He was hugely popular among black audiences throughout The Whole southern U.S. as well as in the Midwestern industrial cities such as Detroit and his home base in Chicago, and his name was synonymous with the blues harmonica for the next decade. Other well-known recordings of his include "Shake the Boogie", "You Better Cut that Out", "Sloppy Drunk", and "Early in the Morning". Williamson's style influenced a large number of blues harmonica performers, including Billy Boy Arnold, Junior Wells, Sonny Terry, Little Walter, and Snooky Pryor among many others. He was easily the most widely heard and influential blues harmonica player of his generation. His music was also influential on many of his non-harmonica playing contemporaries and successors, including Muddy Waters (who had played with Williamson in the mid-1940s) and Jimmy Rogers (whose first recording in 1946 was as a harmonica player, performing an uncanny imitation of Williamson's style); Rogers later recorded Williamson's songs "My Little Machine" and "Sloppy Drunk" on Chess, and Waters recorded "Good Morning Little Schoolgirl" in September 1963 for his Chess LP Folk Singer and again in the 70s when he moved to Johnny Winter's Blue Sky label on CBS.

He was popular enough that by the 1940s, another blues harp player, Aleck/Alex "Rice" Miller, who was based in Helena, Arkansas, began also using the name Sonny Boy Williamson. John Lee is said to have objected to this, though no legal action took place, possibly due to the fact that Miller did not release any records during Williamson's lifetime, and that Williamson played mainly around the Chicago area, and Miller seldom ventured beyond the Mississippi delta region until after Williamson's death. In 1942, John Lee confronted Miller, but according to guitarist Robert Lockwood, "Big Sonny Boy [Miller] chased Little Sonny Boy [Williamson] away from there. He couldn't play with Rice. Rice Miller could play Sonny Boy's stuff better than he could play it!"

Williamson recorded prolifically both as a bandleader and a sideman over the entire course of his career, mainly for the Bluebird record label, with many early sessions taking place in the ballroom on the top floor of the Leland Hotel in Aurora, Illinois; most later sessions were recorded in Chicago. His final recording session took place in December 1947, backing Big Joe Williams. On June 1, 1948, John Lee Williamson was killed in a mugging on Chicago's South Side, as he walked home from his final performance at The Plantation Club at 31st St. and Giles Ave., a tavern just a block and a half away from his home at 3226 S. Giles. Williamson's final words are reported to have been Lord have mercy.

His legacy has been overshadowed in the post-war blues era by the popularity of the musician who appropriated his name, Rice Miller, who after Williamson's death went on to record many popular blues songs for Chicago's Checker Records label and others, and toured Europe several times during the 'blues revival' in the early 1960s.

Williamson is buried at the former site of The Blairs Chapel Church, southwest of Jackson, Tennessee. In 1991, a red granite marker was purchased by fans and family to mark the site of his burial. A Tennessee historical marker, also placed in 1991, indicates the place of his birth and describes his influence on blues music. The historical marker is located south of Jackson on TN Highway 18, at the corner of Caldwell Road.