Benny Goodman, Louis Armstrong, Cab Calloway, Bing Crosby, Bessie Smith, Billy "Uke" Carpenter, Eartha Kitt, Count Basie, Glenn Miller, Guy Lombardo, Peanuts Hucko, Art Tatum, Paul Robeson, and the Boston Pops Orchestra (under the directions of both Arthur Fiedler and Keith Lockhart) are among the artists who have recorded it.

[4] The 1925 version sung by Bessie Smith, with Louis Armstrong on cornet, was inducted into the Grammy Hall of Fame in 1993.

Handy and his Memphis Blues Band was selected by the Library of Congress for preservation in the National Recording Registry in 2023.

[5] Handy said he had been inspired by a chance meeting with a woman on the streets of St. Louis, Missouri, distraught over her husband's absence, who lamented, "Ma man's got a heart like a rock cast in de sea", a key line of the song.

[6] Handy's autobiography recounts his hearing the tune in St. Louis in 1892: "It had numerous one-line verses and they would sing it all night.

[6] Handy said his objective in writing the song was "to combine ragtime syncopation with a real melody in the spiritual tradition.

[16] In 1998, "St. Louis Blues" was included on the album Gershwin's World by Herbie Hancock which featured Stevie Wonder on vocals.