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The working title of this film was The Girl from Cheyenne. While the film's credits and reviews list the characters played by Clare Verdera and Alan Bridge as "Mrs. and Mr. Matthews," the characters are called "Clark" in the film. Universal press materials state that The Lady from Cheyenne was the first film that Frank Lloyd had produced at the studio in approximately twenty-five years. New York Times noted in February 1941 that this was to be the first film of a six-picture deal between Lloyd's Mayfair Productions and Universal. A July 1940 Hollywood Reporter news item states that, after the original story was purchased from writers Jonathan Finn and Theresa Oakes, Lloyd and his partner, Jack H. Skirball, entered into negotiations with actress Carole Lombard to star in the film. In November 1940, Mayfair began negotiations with actress Loretta Young, and on November 28, 1940, Hollywood Reporter confirmed that Young had been signed for the film, which initially was to begin production in late December 1940.
Three weeks after shooting began on January 2, 1941, the production moved to Mojave, CA, where a western town set had been especially constructed for the film. In early February 1941, journalists from twenty newspapers convened in Mojave to report on the location shooting, as part of Universal's publicity endeavors for the film. According to New York Times, since the Mojave location was within three hundred miles of Hollywood, the producers were forced to "bus in" Screen Actor's Guild extras each day, which cost the production an extra $3,600. A February 12, 1941 Hollywood Reporter news item states that actor Tom Chatterton was cast in the film, but his participation in has not been confirmed. Faith Brook, daughter of noted British actor Clive Brook, was reportedly "tested" for an unspecified role in the film in mid-February 1941, but her appearance in the final film also has not been confirmed. New York Times stated in January 1942 that, as a publicity stunt for the film's opening at the Senate Theater in Harrisburg, PA, theater ushers dressed as cowboys and rode horses up and down the aisles. Loretta Young starred with Robert Preston in a June 16, 1941 Lux Radio Theatre broadcast of the story.