In the year 1911, John Marston, a retired outlaw formerly of a gang led by Dutch van der Linde, is taken away from his wife Abigail and his son Jack by government agents. The agents tell Marston that he will be reunited with his family if he hunts down the remaining lead members of his former gang. Left with no choice, Marston travels to the territory of New Austin to capture or kill one of his old friends, Bill Williamson, who now runs his own gang of bandits out of Fort Mercer. Marston confronts Williamson, only to be shot and left for dead outside the fort. A rancher, Bonnie MacFarlane, finds him wounded, and brings him to a doctor to be treated.
After recovering from his wounds several days later, Marston begins repaying the MacFarlanes for their help in the form of several jobs around their ranch. At the same time, he recruits help for a plan to attack Fort Mercer. Along with U.S. Marshal Leigh Johnson of Armadillo and his men, con man Nigel West Dickens, grave robber Seth Briars