In late 1823, fur trapper Hugh Glass guides Captain Andrew Henry's trappers through the territory of the present-day Dakotas. While he and his half-Pawnee son, Hawk, are hunting, the company's camp is attacked by an Arikara war party which is seeking to recover its Chief's abducted daughter, Powaqa. Many of the trappers are killed during the fight, and the rest of them escape onto a boat. Guided by Glass, the survivors travel to Fort Kiowa on foot because Glass believes that traveling downriver will make them vulnerable. After docking, the crew stashes the pelts near the shore.

While he is scouting game, Glass is mauled and left near death by a female grizzly bear which is guarding its cubs. Trapper John Fitzgerald, fearing another Arikara attack, argues that the group must mercy-kill Glass and keep moving. Henry agrees, but he is unable to pull the trigger. Instead, he offers money in order to pay someone to stay with Glass and bury him after he dies. When the only volunteers are Hawk and the young Jim Bridger, Fitzgerald agrees to stay for money, in order to recoup his losses from the abandoned pelts.

After the others leave, Fitzgerald attempts to smother Glass but, afraid that Hawk's loud reaction to his attempt to kill Glass could alert Bridger who is away gathering water, stabs Hawk to death as Glass watches helplessly. The next morning, Fitzgerald convinces Bridger, who is unaware of Hawk's murder, that the Arikara are approaching and they must abandon Glass. At first, Bridger protests, but he ultimately follows Fitzgerald after the latter leaves Glass half-buried alive in a makeshift grave. Bridger leaves his canteen, in which he engraved a spiral symbol, with Glass. After they depart, Fitzgerald admits that he lied about the approaching Arikara. When Fitzgerald and Bridger later meet Henry at the fort, Fitzgerald tells Henry that Glass died and Hawk vanished. Bridger is complicit in the lie about Glass's death, but he knows nothing about Hawk's murder.

Glass begins his arduous journey through the wilderness. He performs a crude cauterization of his wounds and eludes the pursuing Arikara by jumping into river rapids. He later encounters Pawnee refugee Hikuc, who says that "revenge is in the Creator's hands." The men share bison meat and travel. As a storm approaches, Hikuc constructs a makeshift sweat lodge for a feverish Glass to shelter in. After a hallucinogenic experience in the lodge, Glass emerges to discover that his wounds are healing, but French hunters have lynched Hikuc. He infiltrates their camp and sees the leader raping Powaqa. Glass frees her, and while she castrates her rapist, he kills several hunters, and recovers Hikuc's horse. The following day, Glass is ambushed and driven over a cliff on his horse by the Arikara. He survives the stormy night by eviscerating the dead horse and sheltering inside its carcass.

A frightened French survivor staggers into Fort Kiowa, and Bridger recognizes his spiral engraved canteen as Glass's. Believing that it might be a surviving Hawk, Henry organizes a search party. Realizing that Glass is alive, Fitzgerald empties the outpost's safe and flees. The search party finds the exhausted Glass. Furious, Henry orders the arrest of Bridger, but Glass vouches for Bridger by stating that he was not present when Fitzgerald murdered Hawk and he was later deceived and threatened by the higher-ranking Fitzgerald. Glass and Henry set out in pursuit of Fitzgerald.

After the two men split up, Fitzgerald ambushes, kills, and scalps Henry. Glass finds Henry's corpse, places it on his horse in an attempt to act as a decoy, and shoots Fitzgerald in the arm. He pursues Fitzgerald to a riverbank, where they engage in a brutal fight. Glass is about to kill Fitzgerald, but he spots a band of Arikara downstream. He remembers Hikuc's words and pushes Fitzgerald downstream into the hands of the Arikara. Their chief Elk Dog kills and scalps Fitzgerald, and the Arikara (who have found Powaqa) spare Glass. Glass retreats into the mountains, where he is visited by his wife's spirit.