St. Louis Blues is a 1929 American two-reel short film starring Bessie Smith. Directed by Dudley Murphy, it is the only known film featuring Bessie Smith, and the soundtrack is her only recording not controlled by Columbia Records. An early sound film, it features an entirely African American cast, with Smith in the role of a woman left alone by her roving lover; in a speakeasy during the Prohibition era, the woman sings the W. C. Handy standard "St. Louis Blues".

Bessie Smith's recording of Handy's song was a hit in 1925, and Handy himself asked Bessie Smith to appear in the film. Handy co-authored the film and served as its musical director. The film is a dramatization of the song, concerning a woman left alone by her roving man. It features a band that includes James P. Johnson on piano, Thomas Morris and Joe Smith on cornet, Bernard Addison on guitar and banjo, as well as the Hall Johnson Choir.

St. Louis Blues was filmed in June 1929 in Astoria, Queens. The film was rumored for a long time to have been banned as demeaning and to have become lost. Neither rumor was true, but when a print was discovered in Mexico in the 1940s, the event was treated as a significant development, even though copies had, in fact, been available elsewhere.

In 2006, the film was selected for preservation in the United States National Film Registry by the Library of Congress as being "culturally, historically, or aesthetically significant".