Reed Hadley, who plays Frank James, had earlier played brother Jesse in "I Shot Jesse James."
Henry Hull also appeared in "Jesse James' and "The Return of Frank James."
John Ireland, who has first billing as the Jesse James lookalike Johhny Callum, portrayed Jesse James' assassin, Bob Ford, in I Shot Jesse James (1949) which was released one year earlier. The production studio and distributor of both films was Lippert Pictures, which envisioned "The Return of Jesse James" as a sequel to "I Shot Jesse James."
The real Bob Ford died in Colorado in 1892, not in Missouri in 1883, as this film states, and the real Charlie Ford committed suicide in 1886.
There were no Younger brothers named Hank or Lem, as there are in this film.