Robert Mitchum turned down the Tony Curtis' role. Mitchum, a real-life veteran of a Southern chain gang, said that he didn't believe the premise that a black and white man would be chained together, as such a thing would never happen in the very strictly segregated South. Over the years, this reason was corrupted to the point where many people believed Mitchum turned down the role because he didn't want to be chained to a black man, an absolute falsehood. Curtis repeated the inaccurate story in his autobiography, but recanted after it was explained to him.
The film's co-writers, Nedrick Young and Harold Jacob Smith, were cast as the prison truck drivers, with the writing credits below their faces, because Young was blacklisted and writing under a pseudonym at the time and producer Stanley Kramer wanted to identify them truthfully.
Tony Curtis was very keen to make the film as he saw it as an opportunity to break out of the mindless, pretty boy roles he was usually assigned. Director Stanley Kramer initially had some misgivings but ultimately relented.
A joke in industry circles at the time was that Kirk Douglas would only do it if he could play the black convict, and that his frequent co- star Burt Lancaster would only do it if he could play both convicts.
Despite the mutual admiration and camaraderie among the cast and crew, the film wasn't necessarily a breeze to shoot. It was physically exhausting for Tony Curtis and Sidney Poitier, who had to run through fields, swamps, and woods and fight each other barefisted, all while being chained together. There was also the famous climactic run for the train. Most gruelling of all were the scenes where the two chained men are swept down the rapids of a river and their desperate attempt to climb out of a deep clay pit during a rainstorm. Curtis said there were no doubles for the clay pit scene, which he deemed the hardest sequence in the film. He also said he had a stunt double for some of the water scenes while Poitier had a dummy as a stand-in for at least one shot. However, most of the gruelling stunt work was done by the two stars themselves.
Sidney Poitier came to the set with a great deal of respect and admiration for Stanley Kramer. He recalled - "Stanley was always a forerunner of terribly good things; He was the type of man who found it essential to put on the line the things that were important to him. People have short memories: in the days he started making films about important social issues, there were powerful Hollywood columnists who could break careers. He knew this, and he said to himself, 'What the hell', either I do it or I can't live with myself.' For that attitude, we're all in Stanley Kramer's debt. He's an example of the very best of a certain type of filmmaker."
Stanley Kramer originally had Sidney Poitier and Marlon Brando in mind for the two protagonists. Both were interested but only Poitier was available. Brando was caught up in filming Mutiny on the Bounty (1962), a film with a highly troubled and seemingly endless shoot. As the start date for The Defiant Ones (1958) loomed, Kramer had no option but to start looking at other actors. Also, while Brando liked the integration message, he didn't like the way Kramer had produced their film, The Wild One (1953).
Tony Curtis strongly believed in Stanley Kramer and the project, even though he often felt that the director showed favouritism to Sidney Poitier. He recalled - "Because of the racial climate of the time, he went out of his way to be more agreeable to Sidney. I noticed that in his direction and his behaviour. He never treated me with the same reverence he did Sidney. I wasn't mad about it. That's just the way it was. Sidney was a hell of a talent, no matter what colour he was, and this was a time when Hollywood was just starting to realize maybe it could do something positive for civil rights."
Both leads had tremendous praise for the supporting cast. Tony Curtis was particularly excited to be appearing with Carl 'Alfalfa' Switzer, who had been a child star as Alfalfa in the "Our Gang" comedies that Curtis watched as a child. Curtis later said he loved listening to Switzer (an incessant poker-player) talk about being a kid actor in early Hollywood and how he had been swindled out of the money he made from that popular shorts series.
At one point, Sidney Poitier tells Tony Curtis that he used to go to church barefoot. In response, Curtis quips "but all God's children got shoes." This was taken from the popular African-American spiritual "I got Shoes", also called "Heav'n, Heav'n." The full verse goes as follows: "I got shoes, you got shoes, All God's children got shoes. When I get to Heav'n gonna put in my shoes, Gonna walk all over God's Heav'n, Heav'n."