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Bradford grew up in Atlanta, where his family moved when he was six, and in 1906 started working in minstrel shows. He played in Chicago as a solo pianist as early as 1909 and visited New York City the following year.
Through extensive experience with traveling minstrel shows and theatre companies, Bradford obtained exposure to African-American folksongs. Bradford broke down walls of racial prejudice that had kept African-American singers from recording. He has often been unrecognized for this accomplishment. Prior to Bradford's influence, African-American artists recorded in a style that was closely similar to those of white dance orchestras. There was little to no trace of African-American musical characteristics present in their recordings. Bradford persevered in getting the recording industry to value recordings of African-American artists recording in the style of their own subculture.
As a pianist, singer, dancer and composer, Bradford worked in theatre circuits throughout the South and into the North for the next decade (1908–1919) in a song and dance act billed as "Bradford and Jeanette"., While in New York City, Bradford convinced Fred Hager, of Okeh Records, to record Mamie Smith and became her musical director. Smith starred in Bradford's show Made in Harlem (1918). Bradford was also responsible for Smith being the first African-American blues singer to appear on record (singing his "Crazy Blues") in 1920.
Bradford claimed that his revue, Made in Harlem, was the first stage production that offered blues matter to the large, northern audience in Harlem. Bradford was able to organize the first recording session, "That Thing Called Love," that highlighted an African-American artist, accompanied by a white studio band, performing material specific to the African-American culture. 
Bradford toured and recorded with Smith, worked with Alberta Hunter and also headed seven recording sessions of his own during 1923–1927. Among Bradford's sidemen were Johnny Dunn, Bubber Miley, Garvin Bushell, Louis Armstrong (on two numbers in 1925), Buster Bailey, and James P. Johnson.
Bradford continued to promote blues and jazz recordings by publishing and managing. Bradford's influence in the recording industry was negatively affected by the crash of the stock market, as well as by changes in the character of jazz and African-American songs. He was an irregular participant after the 1940s. 
With the rise of the Great Depression, Bradford slipped away into obscurity. In later years, he appeared to exaggerate his role in early blues, possibly a reaction to his being nearly forgotten. In 1957, Little Richard had a hit with Bradford's "Keep A-Knockin'".
In 1965, Bradford's autobiography Born With the Blues was published (New York: Oak Publications) with a foreword by Noble Sissle.
- Welding, Pete (September 1966). "Untitled". Ethnomusicology. University of Illinois Press. pp. 343–45.
- Jazz Dance: The Story of American Vernacular Dance, by Marshall Winslow Stearns, Jean Stearns, Contributor Brenda Bufalino (1994), Da Capo Press, p. 111 ISBN 0-306-80553-7
- Broadway: An Encyclopedia by Ken Bloom – Routledge; 2nd edition (November 11, 2003) ISBN 0-415-93704-3