Musselwhite was born in the rural hill country of Mississippi. He has said that he is of Choctaw descent, and he was born in a region originally inhabited by the Choctaw. However, in a 2005 interview[citation needed], he said his mother had told him he was actually Cherokee. His family considered it normal to play music, with his father playing guitar and harmonica, his mother playing piano, and a relative who was a one-man band. At the age of three, Musselwhite moved to Memphis, Tennessee.