The father of 14-year old Mattie Ross (Hailee Steinfeld) is murdered by hired hand Tom Chaney (Josh Brolin) while on a trip to Fort Smith, Arkansas to purchase horses. While collecting her father’s body, Mattie asks the local sheriff about the search for Chaney. He tells her that Chaney has, likely, fled with “Lucky” Ned Pepper (Barry Pepper) and his gang into Indian Territory, where the sheriff has no authority, so she inquires about hiring a Deputy U.S. Marshal. The sheriff gives three recommendations, and Mattie chooses the “meanest” of the three, Rooster Cogburn (Jeff Bridges). Cogburn initially rebuffs her offer, disbelieving both her grit and her wealth, but she raises the money by aggressively horse-trading with Colonel Stonehill.
Texas Ranger LaBoeuf (Matt Damon) arrives in town, pursuing Chaney for the murder of a Texas State Senator. LaBoeuf proposes joining Cogburn, but Mattie refuses his offer. She wishes Chaney to be hanged in Arkansas for her father’s murder, not in Texas for killing the senator. Mattie insists on traveling with Cogburn but he departs without her, having gone with LaBoeuf to apprehend Chaney and split the reward.
After being refused passage on the ferry that conveyed Cogburn and LaBoeuf, Mattie fearlessly goads her new horse, Blackie, into swimming the river with her. After she successfully crosses, LaBoeuf expresses his displeasure at her obstinance by attempting a spanking with a stick. Cogburn forces him to stop and eventually allows Mattie to accompany them. After a dispute over their respective service with the Confederate Army, Cogburn ends their arrangement and LaBoeuf leaves to pursue Chaney on his own. Cogburn and Mattie meet a trail doctor who directs them to a supposedly empty dugout for shelter. At the dugout, they find two outlaws, Quincy (Paul Rae) and Moon (Domhnall Gleeson), likely waiting for the rest of the Pepper gang. After literally ‘smoking’ the two out, Cogburn and Mattie capture and interrogate them. Quincy insists they have no information about the Pepper gang. Eventually, however, the injured Moon, seems to be about to divulge what he knows whereupon Quincy stabs him in the chest, and Cogburn shoots Quincy dead. Before dying, Moon asks that his body be relayed to his brother and says Pepper and his gang will be returning for fresh horses that night.
Cogburn and Mattie wait on the hillside above the dugout for the arrival of Ned Pepper and his gang. However, LaBoeuf arrives first and then is confronted by the arrival of the Pepper gang. Cogburn shoots two gang members and accidentally hits LaBoeuf, but Pepper escapes. LaBoeuf is injured in the shoulder and in the fall from his horse nearly bites his own tongue off.
With Pepper gone, and LaBoeuf injured, and finding the gang’s stash of whiskey, Cogburn begins to drink heavily. After a few days of steady drinking, Cogburn bows out and tells LaBoeuf and Mattie to continue without him. Mattie tells LaBoeuf that she misjudged him and that she chose the wrong man to pursue Chaney. LaBoeuf tells her that she has proven her grit, and he leaves the posse the next morning.
While retrieving water from a stream, Mattie encounters Chaney. She wounds him with the first shot from her revolver, but when she attempts to shoot him a second time, her wet gun does not fire, allowing Chaney to drag her back to Pepper, who forces Cogburn to leave by threatening to kill her. Pepper leaves Mattie alone with Chaney, ordering him not to harm her or he will not get paid after his remount arrives.
Chaney tries to knife Mattie, but LaBoeuf appears and knocks Chaney out. They watch from a distance as Cogburn fights the remaining members of Pepper’s gang, killing two and wounding Ned before his horse is shot and falls, trapping his leg, whereupon LaBoeuf snipes Pepper. Chaney regains consciousness and knocks out LaBoeuf, but Mattie seizes LaBoeuf’s rifle and shoots Chaney in the chest, killing him. The recoil knocks her into a cave, where she is bitten by a rattlesnake. Cogburn arrives after a time and, lowering himself into the cave, shoots the snakes and cuts into her hand to suck out as much of the venom as he can. Cogburn then promises to send help for LaBoeuf before riding day and night to reach a doctor. Mattie begins to hallucinate Chaney riding ahead of them just out of reach. After Mattie’s horse collapses from exhaustion, Cogburn shoots it over her incoherent objections and begins carrying her on foot. Upon reaching a general store they had visited earlier, he fires in the air to get the owner’s attention and collapses.
Twenty-five years later, Mattie receives a note from Cogburn inviting her to attend a traveling Wild West show in which he is performing. After he brought her to the general store, her left forearm was amputated due to gangrene from the snakebite. He stayed until she was out of danger, but left before she regained consciousness; she has not seen either him or LaBoeuf since then, despite sending an invitation for Cogburn to collect the money she owes him. When she arrives at the show site, she learns that Cogburn died three days earlier. She has his body moved to her family cemetery and stands over the grave, reflecting on this decision, her choice not to marry, and her hope of hearing from LaBoeuf again if he is still alive.