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The film opens with the following written prologue: "The Margaret of this story is real. She hopes, with the rest of us, for ever lasting peace after the war is won. This picture is dedicated to her. This is a small dedication. The great dedication is being made by millions of men and women who are fighting on far-flung battlefronts for all the Margarets of the world." According to a November 1941 Hollywood Reporter news item, William L. White's novel was based on an account by the author and his wife of their experiences adopting an orphan in London where White worked as an American correspondent during the London blitz. According to M-G-M production notes contained in the AMPAS Library file on the film, White's factual account of the adoption had been previously published in Reader's Digest and Life.
The opening onscreen credit order varies slightly from that of the closing credits. Margaret O'Brien's opening credit reads "and presenting Margaret O'Brien as Margaret" and appears after William Severn's name. Although Hollywood Reporter production charts list Herbert Kline as director during the first two weeks of production, he was then replaced by W. S. Van Dyke. According to a June 9, 1942 Hollywood Reporter news item, Kline wanted Dorothy Comingore for the role of "Anya." Although CBCS, Hollywood Reporter production charts and news items list Signe Hasso in the role of Anya, neither she nor the character appeared in the released film. Journey for Margaret would have marked the American motion picture debut of the Swedish-born Hasso, but her first appearance was in the 1943 M-G-M film Assignment in Brittany in 1943. A March 1942 Hollywood Reporter news item adds that Carolyn Lee was considered for a lead in the film. An M-G-M news item hat Sam Marx was originally to produce the picture. Although various Hollywood Reporter news items add George Kirby, Mary Alice Moore, Tom Murray, Bud Penny, Arthur Lovejoy and Ginny Wren to the cast, their appearance in the released film has not been confirmed.