Charles's recording hit number one for two weeks on the Billboard Hot 100, beginning on Monday, October 9, 1961. "Hit the Road Jack" won a Grammy award for Best Rhythm and Blues Recording. The song was number one on the R&B Sides chart for five weeks, thereby becoming Charles's sixth number one on that chart. The song is ranked number 387 on Rolling Stone magazine's list of "The 500 Greatest Songs of All Time".
References in popular culture, cover versions, and usage in media
The Buffalo Bill episode "Hit the Road, Newdell" includes a dream sequence where Dabney Coleman's character lipsyncs the Ray Charles version of the song. This musical sequence was deleted from the DVD release because producers were unable to secure rights to include the song.
In the Two and a Half Men episode "A Bottle of Wine and a Jackhammer", Charlie plays the piece in delight on his piano as Alan moves out of his house.
During the late 1980s and early 1990s, Kentucky Fried Chicken released a series of TV commercials that used a rerecorded version of the song, re-titled "Cross the Road Jack"; additionally, the line "and don't you come back no more" was also changed to "Kentucky Fried Chicken's got more".
The song is included in the 2015 dance exergame Just Dance 2016 as an in-house cover production under the pseudonym "Charles Percy", presumably from the names of Ray Charles, the singer who popularized the tune, and Percy Mayfield, the song's composer.
In the 2016 film Deadpool it is briefly played while Wade Wilson was in a garbage truck.