The song began life in 1930 as a nine-bar phrase with the working title "There's No Stopping Me Now". Its title phrase "Nice work if you can get it" came from an English magazine. It was one of nine songs George Gershwin wrote for the movie A Damsel in Distress in which it was performed by Fred Astaire with backing vocals by The Stafford Sisters. The song was published in 1937.

The first jazz recording of the work was by Tommy Dorsey three weeks after the release of the film.[2] Early chart versions were by Shep Fields, Teddy Wilson with Billie Holiday, Fred Astaire, Maxine Sullivan, and The Andrews Sisters.[3] The song was recorded by many jazz singers and adopted by bebop instrumentalists; Jerry Newman recorded pianist Thelonious Monk performing the tune in 1941 at Minton's Playhouse, a nightclub closely connected with early bebop, and he subsequently recorded it several times. Other jazz pianists who have recorded the tune include Art Tatum in 1949, Erroll Garner in 1968, and Jessica Williams in 1992.

A version of this song was used during the opening credits of the 1995 to 1998 CBS sitcom Cybill, starring Cybill Shepherd, who performed the song. The song was included in the Tony Award-winning Broadway musical Crazy for You and lent its name to the musical Nice Work If You Can Get It.