Peter Joe Clayton, known professionally as Doctor Clayton, was born on April 19, 1898, in Georgia. Despite later claiming African origins, he spent his childhood in St. Louis, where he moved with his family. Clayton worked in a factory and began his singing career there, although he could play piano and ukulele, he never recorded with these instruments.

In 1935, Clayton recorded six sides for Bluebird Records, but only two were released. Tragedy struck in 1937 when his entire family perished in a house fire, leading Clayton to alcoholism. He became known for wearing outsized hats and glasses. Seeking to advance his music career, he relocated to Chicago with Robert Lockwood and gained the attention of Decca Records, aided by Charley Jordan's recommendation. However, he returned to Bluebird Records in 1941-42, recording with Lockwood, bassist Robert Knowling, pianist Blind John Davis, and producer Lester Melrose. He also recorded for Okeh Records during this period.

Clayton was a prolific songwriter, penning "Cheating and Lying Blues," "Pearl Harbor Blues," and "Moonshine Woman Blues," the latter becoming a hit for B.B. King as "The Woman I Love" in 1968. His 1946 recordings included "Hold That Train, Conductor" and "I Need My Baby," both later covered by King. His recordings often featured Blind John Davis on piano, and he found regional success, performing regularly in Chicago nightclubs with Lockwood and Sunnyland Slim. Slim even recorded as "Dr. Clayton's Buddy" in 1947, and Willie Long Time Smith paid tribute with "My Buddy Doctor Clayton."

Doctor Clayton passed away from tuberculosis on January 7, 1947, in Chicago and was buried at Restvale Cemetery in Alsip, Illinois. His funeral was attended by notable musicians Big Bill Broonzy and Tampa Red. Document Records compiled Clayton's works from 1935 to 1942 on a CD, while Old Tramp Records released his 1946 recordings. Despite his relatively short career, Clayton's influence on blues and early rock & roll was significant, impacting artists like Wynonie Harris, B.B. King, and Professor Longhair.