Born of part Cherokee ancestry in Carbondale, Illinois, United States,[1] Trumbauer grew up in St Louis, Missouri, the son of a musical mother who directed saxophone and theater orchestras.

His first important professional engagements were with the Edgar Benson and Ray Miller bands, shortly followed by the Mound City Blue Blowers, a local group that became nationally famous through their recordings on Brunswick.

[1] After leaving Goldkette, he and Beiderbecke worked briefly in Adrian Rollini's short lived New Yorkers band, then joined Paul Whiteman in 1927.

[1] The same year, Trumbauer signed a contract with OKeh and released a 78 recording of "Singin' the Blues", featuring Beiderbecke on cornet and Eddie Lang on guitar.

During 1934–1936, while again a member of Paul Whiteman's Orchestra, he also made a series of recordings for Brunswick and Victor, often including Jack Teagarden.

[1] In 1936 he led The Three T's, featuring the Teagarden brothers; in 1938, he and Mannie Klein started a band which they co-led; he billed himself as "Frank Trombar.

[1] During World War II he was a test pilot with North American Aviation, and trained military crews in the operation of the B-25 Mitchell bomber.

[5] "Singin' the Blues", released by Frankie Trumbauer and His Orchestra featuring Bix Beiderbecke on cornet and Eddie Lang on guitar in 1927 as Okeh 40772-B, was inducted into the Grammy Hall of Fame in 1977.

In 2008, his recordings of "Ostrich Walk" and "There'll Come a Time" with Bix Beiderbecke were included on the soundtrack to the Brad Pitt movie The Curious Case of Benjamin Button, which was nominated for 13 Academy Awards, based on the F. Scott Fitzgerald short story from Tales of the Jazz Age.