Years earlier Richard Widmark had the historical subject matter researched at Yale. He brought the material to John Ford, who didn't want to make it. Years later Ford, who had kept the research, changed his mind and asked Widmark to star.
The final duel between Little Wolf and Red Shirt was shot on the day that President John F. Kennedy was assassinated in Dallas, TX. Though legends say that John Ford, so saddened by the death of the first Irish-descended president of the nation, mourned his death by halting the shoot on that day, production documents actually show that it was the only scene to be shot that day, and they moved from Utah in the afternoon as originally scheduled.
When film critic Peter Bogdanovich visited the set to interview John Ford, he was introduced to Nancy Hsueh, who played Little Bird, whom Bogdanovich later cast in his first film, Targets (1968). While Bogdanovich was on the set, Sal Mineo recommended the book "The Last Picture Show" by Larry McMurtry to him. Seven years later Bogdanovich brought the book to the screen, as his second film, The Last Picture Show (1971). Ben Johnson, who appears in this film, also appeared in "The Last Picture Show", for which he won an Academy Award.
Little Wolf was a chief of the Cheyenne tribe in 1878. He and another chief led the Cheyenne off their Oklahoma reservation and took them back to their homeland in Montana, despite hundreds of US cavalry troops trying to stop them. This was called the "Cheyenne Autumn Trail" and is the basis for this film.
Spencer Tracy was first cast as the secretary of interior Karl Shultz, but had a heart attack and was replaced by Edward G. Robinson, whose scenes were entirely photographed in studios, including the climatic meeting scene between Shultz and the Cheyenne chiefs, in which the background had to be done with screen process.
The role of Lt. Scott was originally offered to Jeffrey Hunter, who turned it town in order to star in the TV series Temple Houston (1963). The part was eventually given to Patrick Wayne. Hunter's series only ran for one season before it was cancelled.
According to both John Ford and James Stewart, Ford added the segment with Stewart in place of an intermission. Ford didn't want people leaving the auditorium to go the bathroom or concessions counter, even though the film was long, and so he came up with the Wyatt Earp segment. He later quipped to Stewart that the actor was the "best intermission" in the movies.
On the set of this movie, Sal Mineo recommended to Peter Bogdanovich the book 'The Last Picture Show', by Larry McMurtrey. Bogdanovich would direct that movie several years later, starring Ben Johnson, who also appeared in 'Cheyenne Autumn.'