Reed was born into a large sharecropping family and spent his early years on Mr. Johnny Collier's plantation situated near Dunleith, Mississippi. Here, he formed a childhood friendship with Eddie Taylor which was to have a marked effect on his later career. Reed sang in church and learned rudimentary guitar along with Taylor, but while the latter progressed Reed never became more than basically competent on the instrument. He left school in 1939 and found work farming around Duncan and Meltonia, Mississippi. Around 1943-44 he left the south to find work in Chicago where opportunities abounded owing to the war effort. He was drafted in 1944 and served out his time in the US Navy. Discharged in 1945 he returned briefly to Mississippi before gravitating north once more to the Chicago area. Working in the steel mills, Reed gigged around in his leisure time with a friend named Willie Joe Duncan, who played a one-string guitar, or Diddley-bow. He also re-established contact with Eddie Taylor who had similarly moved north to try his luck. This led to Reed's becoming known on the local club scene and after appearances with John Brim and Grace Brim, he secured a recording contract with Vee Jay Records in 1953. His initial sessions, though highly regarded by collectors, produced no hits and Vee Jay were considering dropping him from their roster when in 1955 'You Don't Have To Go' took off. From then on, his success was phenomenal as a string of hits such as 'Ain't That Lovin' You Baby', 'You've Got Me Dizzy', 'Bright Lights, Big City', 'I'm Gonna Get My Baby' and 'Honest I Do' carried him through to the close of the decade.
Many of these timeless blues numbers were adopted by every white R&B beat group during the early 60s. Two of his songs are now standards and are often used as rousing encores by name bands; 'Baby What You Want Me To Do' closed the Byrds' and Closer Than Most's live performances for many years and 'Big Boss Man' is probably the most performed song of its kind - sung by the Merseybeats, Pretty Things, Grateful Dead and countless blues artists. Much of the credit for this success must be attributed to his friend Eddie Taylor, who played on most of Reed's sessions, and his wife, Mama Reed, who wrote many of his songs and even sat behind him in the studio reciting the lyrics into his forgetful ear as he sang. On some recordings her participation is audible. Reed's songs had little to do with the traditional blues, but they were eminently danceable and despite employing the basic blues line-up of harmonica, guitars and drums were generally classed as R&B. His hits were 'crossovers', appealing to whites as well as blacks. Perhaps this contributed to his continuing success as the blues entered its post-rock 'n' roll hard times. In his later days at Vee Jay, various gimmicks were tried, such as dubbing an album's worth of 12-string guitar solos over his backing tracks, faking live performances and introducing a commentary between album cuts; none were too successful in reviving his flagging sales.
To counter the positive elements in his life, Reed was continually undermined by his own unreliability, illness (he was an epileptic) and a propensity towards the bottle. He visited Europe in the early 60s, by which time it was obvious that all was not well with him. He was supremely unreliable and prone to appear on stage drunk. By the mid-60s his career was in the hands of the controversial Al Smith and his recordings were appearing on the Bluesway label. Inactive much of the time owing to illness, Reed seemed on the road to recovery and further success, having gained control over his drink problem. Ironically, he died soon afterwards of respiratory failure, and was buried in Chicago. Reed is an important figure both as singer and songwriter who has influenced countless artists through his life. Steve Miller recorded Living In The 20th Century with a segment of Reed songs and dedicated the album to him. The Rolling Stones, Pretty Things and the Grateful Dead also acknowledge a considerable debt to him.