Born Robert Lee Burnside, was a North Mississippi hill country blues singer, songwriter, and guitarist who lived much of his life in and around Holly Springs, Mississippi. He played music for much of his life, but did not receive much attention until the early 1990s.

R.L. Burnside was born in Harmontown, Mississippi, in Lafayette County. He spent most of his life in North Mississippi, working as a sharecropper and a commercial fisherman, as well as playing guitar at weekend house parties. He was first inspired to pick up the guitar in his early twenties, after hearing the 1948 John Lee Hooker single, "Boogie Chillen" (which inspired numerous other rural bluesmen, among them Buddy Guy, to start playing). He learned music largely from Mississippi Fred McDowell, who lived nearby in an adjoining county. He also cited his cousin-in-law, Muddy Waters, as an influence.
During the 1950s, Burnside grew tired of sharecropping and moved to Chicago in the hope of finding better economic opportunities. But things did not turn out as he had hoped. Within the span of one year his father, brother, and uncle were all murdered in the city, a tragedy that Burnside would later draw upon in his work, particularly in his interpretation of Skip James's "Hard Time Killing Floor" and the talking blues "R.L.'s Story", the opening and closing tracks on Burnside's 2000 album, Wish I Was In Heaven Sitting Down.