Orson Welles was John Ford's original choice to play Frank Skeffington, but Welles either lost or refused the part after Ward Bond, a Ford friend and an ultra-conservative Republican, publicly questioned Welles' loyalty to the U.S., as Welles was well known as a progressive Democrat. Ford was furious with Bond, since Welles and Ford were fans of each other's work.
A large exterior set of "Boston row houses" was constructed on the Columbia (now Warner Bros.) Ranch in Burbank for this film. Most of it burned down in 1974 but the Skeffington house survived.
Spencer Tracy said during filming, "I've joked about retiring but this could be the picture. I'm superstitious you know that's a part of being Irish and I'm back with John Ford again, for the first time since I started out with him twenty-eight years ago. I feel this is the proper place for me to end. Even the title is prophetic."
Many thought that Spencer Tracy would get an Oscar nomination for his performance. He was instead nominated for The Old Man and the Sea (1958). Tracy thought his performance in this film was superior.
Early in the film Skeffington says that his signature will never be as valuable as Button Gwinnett's, who apparently had publicly signed few documents in his life. Gwinnett, a delegate from Georgia, was the second signer of the Declaration of Independence, after John Hancock. Gwinnett's signature is quite rare and is considered the most valuable American signature by collectors, with sales recorded as high as $150,000, matched or exceeded only just behind signatures of Gaio Giulio Cesare (aka Julius Caesar) and William Shakespeare. However, it is not quite so rare as suggested by Skeffington, as there are at least 51 examples of Gwinnett's signature known to exist, and at one time during the 1920s five samples of his signature were owned by a dealer in rare books, Dr. A.S.W. Rosenbach.