Portis’s novel is narrated by Mattie Ross, a thrifty, churchgoing elderly spinster distinguished by intelligence, independence, and strength of mind. She recounts the story of her adventures many years earlier, at the age of fourteen, when she undertook a quest to avenge her father’s death at the hands of a drifter named Tom Chaney. She is joined on her quest by Marshal Reuben J. "Rooster" Cogburn and a Texas Ranger named LaBoeuf (pronounced "La-beef").
As Mattie's tale begins, Chaney is employed on the Ross’s family farm in west central Arkansas, near the town of Dardanelle in Yell County. Chaney is not adept as a farmhand, and Mattie has only scorn for him, referring to him as "trash", and noting that her kind-hearted father Frank only hired him out of pity. One day, Frank Ross and Chaney go to Fort Smith to buy some horses. Ross takes $250 with him to pay for the horses, along with two gold pieces that he always carried, but he ends up spending only $100 on the horses. Later, Ross tries to intervene in a barroom confrontation involving Chaney. Chaney kills him, robs the body of the remaining $150 and two gold pieces, and flees into Indian Territory (present day Oklahoma) on his horse.
Mattie hears that Chaney has joined an outlaw gang led by the infamous "Lucky" Ned Pepper and wishes to track down the killer. Upon arriving at Fort Smith, she looks for the toughest deputy U.S. Marshal in the district. That man turns out to be Reuben J. "Rooster" Cogburn, an aging, one-eyed, overweight, trigger-happy, hard-drinking man. Mattie is convinced that he has "grit", and that he is best suited for the job, due to his reputation for violence.
Playing on Cogburn's need for money, Mattie persuades him to take on the job, insisting that she accompany him as part of the bargain. During their preparation, a Texas Ranger named LaBoeuf appears. He has been tracking Chaney for four months for killing a senator and his dog in Texas, and he hopes to bring him back to Texas dead or alive for a cash reward. Cogburn and LaBoeuf take a dislike to each other, but after some haggling, they agree to join forces in the hunt, realizing that they can both benefit from each other's respective talents and knowledge. Once they reach a deal, the two men attempt to leave Mattie behind, but she proves more tenacious than they had expected. They repeatedly try to lose her, but she persists in following them and seeing her transaction with Marshal Cogburn through to the end. Eventually, she is jumped by Cogburn and LaBoeuf, who had hid themselves from view, and LaBoeuf begins to spank Mattie. Mattie appeals to Cogburn and he orders LaBoeuf to stop. At this point, Mattie is allowed to join their posse.
Together, but with very different motivations, the three ride into the wilderness to confront Ned Pepper's gang. Along the way, they develop an appreciation for one another.