George Clooney (Everett) was going to sing the song "Man of Constant Sorrow" for the film but it turned out that he was rather awful, so he ended up lip-synching the songs instead. He said "I'm not my aunt [referring to the late singer/actress Rosemary Clooney, best known for her role in "A White Christmas" (1954)]. I decided it would be easier to just do a passionate lip-sync." He was so nervous that the tapes of his singing would get out that he returned to the studio to make sure all of the evidence had been erased. The musical director of the film confirmed this but said "George is a very good singer but that style of music is very difficult and one almost has to grow up singing it in order to sing it convincingly. George did a really good version of the tune but it wasn't as good as he wanted."

When Everett asks the hobos on the train if any of them are "smithys", look closely and you'll see that they're sitting on big bags of Pappy O'Daniel flour. Pappy is a major character later in the film.

The soundtrack to the film was more successful than the film itself. It sold over five million copies and inspired a minor cult following.

Tommy Johnson was a real bluesman of the time, who was rumored to have sold his soul to the Devil. He was supposed to have met the Devil by "the crossroads", where in fact Everett & co first meet him. While this is also true about Robert Johnson, the character in the movie was always supposed to be Tommy (who also contributed actively to spreading the rumor for the PR value, unlike Robert).

Just like the classical Odysseus, Everett openly defies God, and has constant troubles because of it. The second he repents and asks for God's help he is saved from death and everything turns out OK.

The man with the hound that represents the devil tracks down Everett by the scent of his pomade. This is similar to another Joel and Ethan Coen movie, "Raising Arizona," in which the biker tracks H.I. by using the scent of Gale's pomade.

In the opening credits it says that this movie is based on Homer's Odyssey. This is meant to be a joke, but you can actually find some references to the Odyssey. For instance, Big Dan Teague has only one good eye. In the Odyssey, Odysseus (the hero of the Odyssey) kills a cyclops. Another tribute to the Odyssey is the three women that are singing and washing clothes. These characters are based on the Sirens, women who live underwater and sing a song that enchants men. Also, in this movie Everett is trying to get back to Ithaca, Mississippi. In the Odyssey, Odysseus is trying to get back to Ithaca, Greece. Even Homer(the writer of the Odyssey) makes an "appearance" during the film. You can see a statue of Homer in the background when the candidate running for Governor is in that nice restaurant that Everett and Delmar just left.

Another reference to "The Odyssey": The name Odysseus means "man of constant sorrow", the song sung by the Soggy Bottom Boys.

In Preston Sturges' famous comedy Sullivan's Travels, the film director played by Joel McCrea is tired of making screwball comedies and wants to shoot a serious film about the Depression. The title he has chosen is "Oh Brother, Where Art Thou?". Hence the title of the Coen Bros. film.