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The working titles of this film were Operation Moon and Journey to the Moon. At the end of the film, the following words appear onscreen: "This is the end/of the beginning." According to the Screen Achievements Bulletin, which was signed by George Pal, director Irving Pichel did a considerable amount of work on the screenplay, although he is not credited onscreen for this contribution. Pal chose to hire relatively unknown actors for the picture, fearing that famous or typecast performers would detract from the story's credibility. According to a August 1, 1949 Los Angeles Times news item, Pal scouted small legitimate theaters throughout the country, accompanied by his associate Harry Henkle and film editor Duke Goldstone.
According to information contained in the film's production file at the AMPAS Library, pre-production work took more than a year and included consultations with military rocket engineers and scientists from California Institute of Technology. Photographs taken from the Palomar Observatory in San Diego were used to create the set for the moon. The film won an Academy Award for Best Special Effects and was nominated for Best Art Direction (Color). The film's special effects included miniatures, stop-frame animation and makeup devices to simulate the effect of gravitational pull on the actors' faces. It also received the Bronze Bear at the Berlin Film Festival. Destination Moon was Eagle Lion Classics' highest-grossing film of 1950.
Modern sources cite the film as a milestone in the development of the science fiction genre, noting that it portrayed space travel with unprecedented realism. The production marked the motion picture debut of comic actor Dick Wesson.