He was born in Louisville, Kentucky, and moved to Chicago around 1916, studying with pianist Clarence Jones. He was an all-round pianist, who generally incorporated boogie woogie styles into more varied pieces such as "Chicago Stomps" (1924) which drew on ragtime and other popular styles of the time.

He made eight solo piano rolls in the early 1920s, before accompanying many singers on Paramount Records and appearing with small "spasm bands" like the Midnight Rounders and the State Street Ramblers. He also duetted with Johnny Dodds, and led his own group, "Blythe's Sinful Five". His 1925 recording, "Jimmy's Blues", provided the theme used by Clarence "Pine Top" Smith on the classic "Pine Top's Boogie Woogie", and he was also acknowledged as an influence by Albert Ammons.

Blythe died of meningitis in Chicago in 1931, aged 30

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