Fox purchased the screen rights to the novel in March 1945 for $250,000 plus 20% of the net profits. To avoid another $50,000 specified in the contract if the principle photography was not started by 2 February 1946, producer Darryl F. Zanuck provided for location shooting in the mountains around Denver, Colorado (the Himalayas in the film) in August 1945. The cast had not yet been set, so the character of Larry was played by a double and seen only in long-shot. Zanuck hoped to get 'Tyrone Power (I)' to star and delayed casting until Power was released from military service in Januay 1946.
Gene Tierney was Maugham's original choice for Isabel but Zanuck cast Maureen O'Hara instead. According to O'Hara, Zanuck told her to keep it a secret but she told Linda Darnell. Zanuck found out, fired O'Hara, and hired Tierney.
When filming the hospital scene, Anne Baxter drew upon an experience from her childhood, when she lost her three-year-old brother. Speaking of it years later, she said the scene was the best in her career, and still gave her chills.
89 different sets were built for the film, which had the longest shooting schedule for any film at the studio to that date. According to some news items, the film broke all previous studio box office records.
Alexander Knox, Anne Revere, Marcel Dalio, and Philip Merivale (who was actually born in India) were earlier choices for the roles played by Herbert Marshall, Elsa Lanchester, Robert Barron, and Cecil Humphreys.
Although Fox did not use Somerset Maugham's screen adaptation of his own novel, it felt it owed the author something. George Cukor suggested giving him a fine modern painting, which the director later recalled was a Matisse.