It stars jazz and blues greats Nat "King" Cole, Pearl Bailey, Cab Calloway, Ella Fitzgerald, Eartha Kitt, and Barney Bigard, as well as gospel singer Mahalia Jackson and actress Ruby Dee.

In conjunction with the film, Cole recorded an album of W. C. Handy compositions, arranged by Nelson Riddle, and Fitzgerald incorporated "St. Louis Blues" into her concert repertoire.

His father, the Reverend Charles Handy (Juano Hernandez) rejects all music other than church hymns as songs of Satan, and destroys the trumpet upon discovery.

Handy is offered a teaching job his family approves of, but volunteers instead to write music for a local political campaign, drawing the attention of singer Gogo Germaine (Eartha Kitt) and nightclub owner Blade (Cab Calloway).

After going blind and subsequently abandoning his jazz career, Handy returns to performing in his church and composing hymns, finally winning the approval of his father.