The book was quickly made into a famed, 1940 Hollywood movie of the same name directed by John Ford and starring Henry Fonda as Tom Joad. The first part of the film version follows the book fairly accurately. However, the second half and the ending, in particular, differ significantly from the book. John Springer, author of The Fondas (Citadel, 1973), said of Henry Fonda and his role in film version of The Grapes of Wrath: "The Great American Novel made one of the few enduring Great American Motion Pictures."
The documentary American: The Bill Hicks Story (2009) revealed that The Grapes of Wrath was comedian Bill Hicks' favorite novel. He based his famous last words on Tom Joad's final speech: "I left in love, in laughter, and in truth, and wherever truth, love and laughter abide, I am there in spirit."
In July 2013, Steven Spielberg announced his plans to direct a remake of The Grapes of Wrath for DreamWorks.
Woody Guthrie's two-part song—"Tom Joad – Parts 1 & 2" – from the album Dust Bowl Ballads (1940), explores the protagonist's life after being paroled from prison. It was covered in 1988 by Andy Irvine, who recorded both parts as a single song—"Tom Joad"—on Patrick Street's second album, No. 2 Patrick Street.
The song "Here Comes that Rainbow Again" by Kris Kristofferson (1981) is based on the scene in the roadside diner where Pa Joad buys a loaf of bread and two candy sticks for Ruthie and Winfield.
The band The Mission UK included a song, titled "The Grapes of Wrath", in their album Carved in Sand (1990).
The progressive rock band Camel released an album, titled Dust and Dreams (1991), inspired by the novel.
American rock singer-songwriter Bruce Springsteen named his 11th studio album, The Ghost of Tom Joad (1995), after the character. The first track on the album is titled "The Ghost of Tom Joad". The song – and to a lesser extent, the other songs on the album – draws comparisons between the Dust Bowl and modern times.
Rage Against the Machine recorded a version of "The Ghost of Tom Joad" in 1997.
Like Andy Irvine in 1988, Dick Gaughan recorded Woody Guthrie's "Tom Joad" on his album Outlaws & Dreamers (2001).
An opera based on the novel was co-produced by the Minnesota Opera, and Utah Symphony and Opera, with music by Ricky Ian Gordon and libretto by Michael Korie. The opera made its world premiere in February 2007, to favorable local reviews.
Bad Religion have a song entitled "Grains of Wrath" on their album, New Maps of Hell (2007). Bad Religion lead vocalist, Greg Graffin, is a fan of Steinbeck's.
The song "Dust Bowl Dance" on Mumford & Sons' album Sigh No More (2009) is based on the novel.
Pink Floyd's song "Sorrow", written by David Gilmour, from the album A Momentary Lapse of Reason is thematically derived/based on the novel.
The Steppenwolf Theatre Company produced a stage version of the book, adapted by Frank Galati. Gary Sinise played Tom Joad for its entire run of 188 performances on Broadway in 1990. One of these performances was filmed and shown on PBS the following year.
In 1990, the Illegitimate Players theater company in Chicago produced Of Grapes and Nuts, an original, satirical mash-up of The Grapes of Wrath and Steinbeck's acclaimed novella Of Mice and Men.