The film is sometimes called "An RKO Radioactive Picture." Exteriors were shot in the Escalante Desert near St. George, Utah, which is 137 miles downwind of the United States government's Nevada National Security Site and received the brunt of nuclear fallout from active atomic weapons testing in this period. In 1953, two years before production started, 11 above-ground nuclear weapon tests occurred at the Nevada site as part of Operation Upshot-Knothole. The cast and crew spent many difficult weeks on the Utah location. The filmmakers knew about the nuclear tests, but the federal government had assured residents that the tests posed no hazard to the public health. Over 100 above and below ground nuclear bombs were detonated in the area from 1951 to 1962. Although the area was contaminated by nuclear fallout, the Atomic Energy Commission assured Howard Hughes and the local population that the area was completely safe. Photographs exist of John Wayne holding a Geiger counter that reportedly made so much noise that he thought it was broken. After location shooting, Hughes had over 60 tons of contaminated soil transported back to Hollywood in order to match interior shooting done there. Over the next 30 years, 91 of the 220 cast and crew members developed cancer. Forty-six died, including John Wayne, Susan Hayward, Pedro Armendáriz (who shot himself in 1963 soon after learning he had terminal cancer), Agnes Moorehead, John Hoyt, and director Dick Powell. Lee Van Cleef had throat cancer, but died of a heart attack. 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. A "People" 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 article is available in its archive online. It has however been suggested that many of the cast and crew died of cancer as a result of smoking. John Wayne had smoked between three to five packs of cigarettes a day since the early 1930s, and most of the other actors and crew members were also heavy cigarette smokers.
The box-office failure of this movie was ultimately responsible for the demise of RKO Radio Pictures.
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, including paying to ship 60 tons of soil to Hollywood for retakes, unaware it was radioactive. He later paid $12 million for every existing copy because of guilt after many of the cast and crew were diagnosed with cancer. He kept a tight hold on the film, not even allowing it to be shown on television, for years. Universal bought the rights to the film in 1979 and according to "The Hollywood Reporter", it hadn't been seen by the public for 21 years prior to the purchase (allegedly, Paramount obtained reissue rights in 1974). Hughes reportedly called the choice of the film's shooting location the worst mistake of his life.
Many of the Mongol extras were played by local Navajo Indians. They did not wear any makeup.