Burnside spent most of his life in the rural hill country of northern 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, Illinois in the hopes of finding better economic opportunities. But things did not turn out as he had hoped. Within the span of one month 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.
In around 1959 he left Chicago and went back to Mississippi to work the farms and raise a family. Burnside claimed to have been convicted for murder and sentenced to six months’ incarceration for the crime. Burnside’s boss at the time reputedly pulled strings to keep the murder sentence short, due to having need of Burnside’s skills as a tractor driver. "I didn’t mean to kill nobody," Burnside later said. "I just meant to shoot the sonofabitch in the head. Him dying was between him and the Lord."
His earliest recordings were made in the late 1960s by George Mitchell and released on Arhoolie Records. Another album of acoustic material was recorded that year and little else was released before "Hill Country Blues," in the early 1980s. An album’s worth of singles followed, released on ethnomusicology professor Dr. David Evans’ Highwater Records label in Memphis, Tennessee.
In the 1990s, he began recording for the Oxford, Mississippi, label Fat Possum Records. Founded by Living Blues magazine editor Peter Redvers-Lee and Matthew Johnson, the label was dedicated to recording aging North Mississippi bluesmen such as Burnside and his friend Junior Kimbrough. Burnside remained with Fat Possum from that time until his death, and usually performed with his friend and understudy, the slide guitarist Kenny Brown, with whom he began playing in 1971 and claimed as his "adopted son."
In the mid-1990s, Burnside attracted the attention of Jon Spencer, the leader of the Jon Spencer Blues Explosion, touring and recording with this group and gaining a new audience in the process.
Since the death of Kimbrough and the burning of Kimbrough’s juke joint in Chulahoma, Mississippi, Burnside quit recording studio material for Fat Possum, though he did continue to tour. After a heart attack in 2001, Burnside’s doctor advised him to stop drinking; Burnside did, but he reported that change left him unable to play.
Members of his large extended family continue to play blues in the Holly Springs area: grandson Cedric Burnside tours with Kenny Brown, while his son Duwayne Burnside has played guitar with the North Mississippi Allstars (Polaris; Hill Country Revue with R. L. Burnside). Duwayne’s solo career began when "Duwayne Burnside and the Mississippi Mafia" recorded "Live At the Mint" in October 1997. Members included Cedric Burnside, Eddie Batos, Joe Hill from Alien Ant Farm, and David Kimbrough, Jr. (Junior Kimbrough’s son) with Duwayne’s father R. L. sitting in on a few tracks. Duwayne and the Mississippi Mafia released "Under Pressure" in March of 2005, which was recorded at Delta Studios in Clarksdale, Mississippi featuring James Mathus, rhythm guitar (Squirrel Nut Zippers), Roy Cunningham on drums (Stax Sessions), and R. L.’s son Garry Burnside on bass guitar. In 2004, the Burnside sons opened Burnside Blues Cafe, located 30 miles southeast of Memphis at the intersection of U.S. Highway 78 and Mississippi Highway 7 in Holly Springs, Mississippi.
Burnside had been in declining health since heart surgery in 1999, and died in a hospital in Memphis, Tennessee on September 1, 2005 at the age of 78. He is survived by his wife Alice Mae, twelve children (including musicians Duwayne and Garry), and numerous grandchildren.
In January of 2006, Garry and Cedric released "The Record" under the moniker "Burnside Exploration" continuing the musical legacy of R. L.
