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|Lon Chaney Jr.||One of James Gang|
|Henry Fonda||Frank James|
|Nancy Kelly||Zerelda 'Zee' Cobb|
|Randolph Scott||Marshall Will Wright|
|Henry Hull||Major Rufus Cobb|
|J. Edward Bromberg||Mr. Runyan|
|John Carradine||Bob Ford|
|Donald Meek||Mc Coy|
|Johnny Russell||Jesse James Jr. (as John Russell)|
|Jane Darwell||Mrs. Samuels - Jesse's mother|
|Tyrone Power||Jesse Woodson James|
A railroad worker named Barshee (Brian Donlevy) forces farmers to give up the land the railroad was going to go through, giving them $1 per acre (much less than fair price) for it. When they come to Jesse's home, Jesse (Tyrone Power) tells Barshee that his mother Mrs. Samuels (Jane Darwell) is the farm's owner. Barshee repeatedly tries to force her into selling, until her other son Frank James (Henry Fonda) gets involved. Frank fights and easily beats Barshee, but Barshee's men get involved and Jesse shoots him in the hand. When arrest warrants are issued for Frank and Jesse, Major A. Rufus Cobb (Henry Hull) editor in nearby Liberty, Missouri and uncle of Zerelda (Zee) Cobb (Nancy Kelly), Jesse's lover, quickly comes to tell them to leave. Frank and Jesse learn that Barshee is responsible for the death of their mother and Jesse kills him in revenge. This begins Frank and Jesse's career as outlaws. Three years later, with a $5000 on his head, Jesse marries Zee and turns himself in, having been promised a light sentence by Marshall Will Wright (Randolph Scott). But the judge supersedes Marshall Wright's recommendation and Jesse is given a stiff sentence. Frank breaks Jesse out of jail but is captured in the process. Jesse continues his life of crime and eventually Zee leaves him, taking their son Jesse Jr. Years later, a wounded Jesse returns home and Zee joins him in the belief that they will escape to California. Meanwhile, Frank has escaped and sends Bob Ford (John Carradine) to Jesse with a message. But Bob Ford betrays and kills Jesse instead.