The film is sometimes called "An RKO Radioactive Picture." It was filmed near a nuclear test site, and the set was contaminated by nuclear fallout. Photographs exist of John Wayne holding a Geiger counter. After location shooting, contaminated soil was transported back to Hollywood in order to match interior shooting done there. Over the next 20 years, many actors and crew members developed cancer. People Magazine researched the cast and crew's health for an article. By the time it was published, in November 1980, 91 of the 220 cast and crew members had developed cancer. Forty-six had died, including John Wayne, Susan Hayward, Pedro Armendáriz (who shot himself soon after learning he had terminal cancer), Agnes Moorehead, John Hoyt and director Dick Powell. The count did not include several hundred local Native Americans who played extras, or relatives of the cast and crew who visited the set, including John Wayne's son Michael Wayne. The article quoted the reaction of a scientist from the Pentagon's Defense Nuclear Agency to the news, "Please, God, don't let us have killed John Wayne". As of June 2011, the People article is available in their archive online.
John Wayne regretted playing Temujin so much that he visibly shuddered whenever anyone mentioned the film's name. He once remarked that the moral of the film was "not to make an ass of yourself trying to play parts you're not suited for."
Eccentric billionaire Howard Hughes backed the film financially. He later paid an extra $12 million (estimated) for every existing copy because of guilt; he paid to ship 60 tons of contaminated soil to Hollywood for retakes. He kept a tight hold on the film, not even allowing it to be shown on television, for 17 years. Universal finally obtained reissue rights in 1974.
According to "The Hollywood Hall of Shame," the screenplay was written with Marlon Brando in mind for the lead. John Wayne was about to make the last film of a three-picture deal for RKO Radio, and Dick Powell had been assigned to direct. They were going over various scripts in Powell's office when Powell was called away for a few minutes. When he returned, he found Wayne enthusiastically looking over the screenplay for "The Conqueror", which Powell had intended to throw away. Powell tried to talk him out of it, but Wayne insisted that it was the film he wanted to make. As Powell later said, "Who am I to turn down John Wayne?"
The character Wang Khan, played by Thomas Gomez, is also known in history books as Ong Khan, Togrul, Toghrul, or Toghril. He was a member of the little-known Nestorian Christian sect, and European missionaries often referred to him in their reports as Prester John, a popular name for a hypothetical ideal Christian king.
Screenwriter Oscar Millard wrote the script for "The Conqueror" thinking the either Marlin Brando or Richard Burton would be portraying Temujin and reciting his flowery prose in their theatrically trained voices.Both actors wisely passed on the the opportunity to work on the project. Imagine Millard's shock and awe when he learned that the Duke himself was going to give voice to Genghis Khan and that everyone's favorite Brooklyn Irish Colleen Susan Hayward was to play Bortai. He may have been the one to suggest that they shoot so close to the atomic bomb testing sight, maybe hoping that all traces of the film go up in smoke and his reputation would be spared.