McDowell was born in 1906, in Rossville, Tennessee. His parents, who were farmers, died in his youth. He started playing guitar at the age of 14 and played at dances around Rossville.
In 1928 he moved to Mississippi to pick cotton. He finally settled in Como, Mississippi. Initially he played slide guitar, using a pocketknife and then a slide made from a beef rib bone, later switching to a glass slide for its clearer sound. He played with the slide on his ring finger.
Although commonly regarded as a Delta blues singer, McDowell may be considered the first Hill Country blues artist to achieve widespread recognition for his work. Musicians from the hill country – an area parallel to and east of the Delta region – produced a version of the blues somewhat closer in structure to its African roots. It often eschews chord change for the hypnotic effect of the droning single-chord groove.
McDowell was brought to wider public attention, beginning when he was recorded in 1959 by Alan Lomax and Shirley Collins. His records were popular, and he often performed at festivals and clubs.
McDowell continued to perform blues in the north Mississippi style much as he had for decades, but he sometimes performed on electric guitar rather than acoustic.
When the folklorist George Mitchell decided to make the trip to Mississippi to find some blues musicians, he was given Fred McDowell’s name and told that he lived somewhere around Como. Driving down the highway, he pulled into a Stuckeys to get some gas.
Asking the attendant if he knew Fred McDowell – to George’s astonishment the attendant turned around and told him “You’re looking right at him!”