It's right after the American Civil War and a small group of Confederate veterans have returned to their hometown of Liberty, Missouri. Among them are brothers Jesse (COLIN FARRELL) and Frank James (GABRIEL MACHT) who are happy to see their mother (KATHY BATES), and brothers Cole (SCOTT CAAN) and Bob Younger (WILL McCORMACK) who are now reunited with their younger brother, Jim (GREGORY SMITH).
Although Jesse is encouraged by how Zee Mimms (ALI LARTER), daughter of Doc Mimms (RONNIE COX), has grown up, things don't look good for the men and their Confederate companions including Clell Miller (TY O'NEAL), Loni Packwood (JOE STEVENS) and Comanche Tom (NATHANIEL ARCAND).
It seems that a Union garrison now occupies their town and that railroad tycoon, Thaddeus Rains (HARRIS YULIN), of the Rock Island Railroad, is using eminent domain to claim a right of way thoroughfare for his line. For those who don't accept his offer of $2 dollars an acre, Rains' right-hand man, Rollin Parker (TERRY O'QUINN), hired consultant and founder of the Secret Service, Allan Pinkerton (TIMOTHY DALTON), and his men are on hand to take care of any problems should they arise.
They do in the form of the angry farmers who've decided they've had enough of the government and Northerners pushing them around. Accordingly, the farmers form the James-Younger gang and decide to disrupt the railroad company's expansion by robbing it off its money and sabotaging its tracks. The gang soon becomes infamous for their various bank robberies and daring rescues, much to the chagrin of Rains.
From the point on, and as Pinkerton and his men try to track them down and capture the various outlaws, the various members of the James-Younger gang continue with their quest, all while dealing with both internal and external complications that threaten their goal, freedom and lives.