Rickey Medlocke was born on February 17, 1950, in Jacksonville, Florida. He was raised by his maternal grandparents. His grandfather, Shorty Medlocke, was a well-known Delta blues musician and taught his grandson to play a miniature banjo. Medlocke started performing onstage at age three, and his musical abilities increased over the years. He began teaching himself to play the guitar by age five and was playing drums in Shorty's band at age eight. Over the next several years Medlocke mastered the banjo, guitar, drums, mandolin, dobro and keyboards. He had a melodic singing voice and had taught himself to sing and play guitar at the same time. After graduating high school, Medlocke formed his first band, Fresh Garbage (inspired by the Spirit song), in which he was lead vocalist and Drummer. That band soon changed its name to Hammer.

Medlocke recorded shortly with the 1970s era Lynyrd Skynyrd band as a session musician, occasionally playing drums or singing lead on a few songs for them in 1971: "One More Time", "Preacher's Daughter", "Lend a Helpin' Hand", "Wino", "White Dove", "Comin' Home", "The Seasons", "Ain't Too Proud to Pray", and "You Run Around". On occasion, Medlocke played alongside the band's original Drummer Bob Burns but came to Desire the Energy of a Guitarist at the front of the stage. This resulted in his 1972 decision to reform Blackfoot. The band began touring and producing hit songs that included "Train, Train", which was written by his grandfather, and "Highway Song", written by Rickey Medlocke and Blackfoot Drummer Jakson Spires, along with songs written by others. He disbanded the group in the early 1990s.

For a while in the 1990s, Medlocke thought about pursuing other careers until he received a phone call in 1996 from Gary Rossington inviting him to rejoin Lynyrd Skynyrd as a lead Guitarist and primary Songwriter. Rossington asked Medlocke if he remembered how to play "Free Bird", "Tuesday's Gone", and "Workin' For MCA", among others. Medlocke rejoined Skynyrd and has been a member since. Occasionally, Medlocke will step away from Skynyrd briefly to join Musicians like Blackberry Smoke and Shooter Jennings onstage. He joined American Idol finalist Bo Bice on stage for a rendition of "Sweet Home Alabama" when the top three finalists from season four returned home.

Being of Native American ancestry, specifically Lakota Sioux and Cherokee, Medlocke was inducted into the Native American Music Hall of Fame in 2008.