There he lived with his father who had also moved to the city. Though he had put his guitar aside at the time, Burnside nonetheless absorbed the intoxicating sounds of his new environment. He also met Muddy Waters, who had married his first cousin. "I was working during the day at the foundry," he recalled to Kenny Brown of Blues on Stage online, "and every night I'd go over to Muddy's. We only lived a couple of blocks apart." He also caught Waters' Friday night show at the Zanzibar and frequented Mackerel Street on Sundays to hear players like Little Walter, Jimmy Rogers, and Chuck Berry. Tragically, within a year of each other, Burnside's father, uncle, and two brothers were murdered in the late 1940s. Burnside chronicles the losses on Wish I Was in Heaven Sitting Down. Burnside married Alice Mae Taylor in 1949; the couple had 12 children.

During the 1970s and 1980s, Burnside played with Sound Machine, a band consisting of two of his sons, Joseph and Daniel, and then son-in-law Calvin Jackson. His real break would have to wait until the early 1990s, though, when he was featured in former New York Times critic Robert Palmer's documentary, Deep Blues. movie theater must have begun tapping his or her foot."

On Palmer's advice, Matthew Johnson of the fledgling Fat Possum Records sought Burnside out and signed him. In 1991, with Palmer onboard as producer, Bad Luck City was released. Critics warmly embraced Bad Luck City and its follow-up, Too Bad Jim, in 1994. This was down and dirty jukebox blues, deeply felt, and music a listener could dance to. "R.L. Burnside lays down some of the most funky, low down blues coming out of the Delta these days," wrote the Delta Boogie online. Too Bad Jim became one of the most influential blues albums of the 1990s. The music was raw and at times unrehearsed, giving it an immediacy lacking on heavily polished blues albums. "This is unfussy music, hell, it's sloppy in the best way," Nassar noted. Along with artists like Junior Kimbrough, Burnside proved that 1940s and 1950s juke joint blues still had the power to speak to contemporary listeners.

Too Bad Jim also brought Burnside to the attention of Jon Spencer of the Jon Spencer Blues Explosion. These seemingly incongruous players, a bluesman born in the 1920s and a post-punk indie band, joined forces in 1996 to make a record. A Ass Pocket of Whiskey retained the raw, edginess of the earlier Burnside recordings while adding a heavy dose of industrial rock. Some critics loved it. "This is the real stuff--raw, urgent, humorous and spiritual...," wrote George H. Lewis of Popular Music and Society online. Others disliked the change, believing that Jon Spencer's brashness mocked the blues form. The release of Come on In in 1998, complete with trip-hop rhythms provided by producer Tom Rothrock (who also produced Beck's first album), only furthered the controversy for purists. These albums and the video for "Let My Baby Ride," however, also introduced Burnside to a younger audience.

While his latest releases have been more traditional and are less likely to end up on MTV, Burnside continues to receive exposure from "It's Bad You Know," featured on the television series The Sopranos.

Burnside's discography:

Bad Luck City , Fat Possum, 1991.
Deep Blues (soundtrack), Atlantic, 1992.
Too Bad Jim , Fat Possum, 1994.
A Ass Pocket of Whiskey , Matador, 1996.
Mr. Wizard , Fat Possum, 1997.
Come on In , Epitaph, 1998.
Wish I Was in Heaven Sitting Down , Fat Possum, 2000.
Well Well Well , M.C., 2001.
Burnside on Burnside , Fat Possum, 2001.