During the years following the Civil War, banks and trains become the targets of the James-Younger gang, who terrorize the Midwestern United States. The band of robbers is led by Jesse James (James Keach) and Cole Younger (David Carradine), along with several of their brothers. After getting antsy during a bank robbery, Ed Miller (Dennis Quaid) opens fire, killing the clerk and resulting in a shootout where Jesse is wounded. Jesse dismisses Ed from the gang; his brother Clell (Randy Quaid) remains.
A detective, Mr. Rixley from the Pinkerton’s agency, is assigned to capture the outlaws. Rixley doggedly remains on their trail, accidentally killing a Younger cousin and the youngest James brother, and losing several of his men in the process. Due to his errors, the Pinkertons back off. Jim Younger, who initially courted a girl named Beth, is disturbed to find her engaged to Ed. At his younger brother’s funeral, he convinces Beth to leave Ed and she eventually marries him. Clell Miller suggests the James-Younger Gang ride north in September 1876 to rob a bank belonging to “squareheads” in Northfield, Minnesota; word is out about them and the town has been warned by the Pinkertons.
The holdup goes wrong: the bank’s vault has been set on a timer and cannot be opened. A cashier and another citizen are shot and killed. While trying to escape, the gang is fired upon by the townspeople. Two outlaws are killed, Clell is fatally shot, Frank (Stacy Keach) is hit in the arm, and all of the Youngers are badly wounded.
The surviving gang members temporarily make camp in the woods. Jesse decides to continue running, leaving the injured to their fate when a posse catches up to them. Though reluctant and threatened by Cole, Frank joins Jesse and they ride off. Jesse informs Frank he intends to strike up a new gang when they return to Missouri, but Frank is clearly reticent. The James brothers return home to Missouri and the Youngers are captured. Rixley interrogates the Youngers in prison, but they refuse to give up Jesse.
Bob and Charlie Ford offer to give up Jesse, who has asked them to join his new gang, for money. Rixley recruits them to assassinate Jesse for $15,000. They have dinner at Jesse’s house and, while he adjusts a hanging picture, Bob kills him. Upon learning of his brother’s assassination, Frank James turns himself in on the condition he can take Jesse home to be buried. Rixley complies with Frank in custody.