John Ottway (Liam Neeson) is a marksman for an oil company in Alaska, killing grey wolves that threaten the drillers. On his last day on the job, he sees a wolf pursuing a driller and shoots it, listening to the wolf’s final breath. That evening, Ottway writes a letter "without purpose" to his wife, Ana (Anne Openshaw), explaining his plans to commit suicide, but does not follow through.
The next day, Ottway survives a plane crash with fellow oil workers, watching helplessly as Lewenden (James Badge Dale) dies of his injuries. Ottway takes charge of the survivors and is attacked by a wolf and rescued by the group; they realize they are in the wolves' territory and take turns keeping watch.
Hernandez (Ben Bray) is killed by wolves, and Ottway suggests they leave the crash site, but Diaz (Frank Grillo) questions his leadership. While searching for the wallets of the dead to return to their families, Diaz finds an emergency wrist watch with a radio beacon.
The group leaves the crash site, but Flannery (Joe Anderson) falls behind and is killed by wolves. A pack of wolves approaches and the survivors run for the trees, lighting a fire to ward off the animals and building makeshift weaponry. Diaz succumbs to stress and threatens Ottway with a knife but is quickly disarmed. Before he can apologize, he is attacked by a wolf, which the group manages to kill and roast for food. Ottway surmises the wolf was an omega sent by the alpha wolf to test the group. A crazed Diaz beheads the wolf’s corpse, throwing the severed head at the pack.
Diaz tells the group of his atheism and Talget (Dermot Mulroney) states that he believes in God and lovingly talks about his daughter. Ottway says he is also an atheist, but wishes he could believe or have faith, and recites a simple poem written by his father.
A blizzard approaches, and in the morning, Burke (Nonso Anozie), who had been suffering from hypoxia, is found dead. The remaining survivors travel to the edge of a canyon. Hendrick (Dallas Roberts) secures a line to a tree on the opposite side, and Diaz and Ottway traverse the canyon. Talget gets his foot caught on a hook, and the rope breaks away and he falls to the ground. Barely alive, he hallucinates a vision of his daughter, and is dragged away by wolves. Attempting to save Talget, Diaz falls from the tree and badly injures his knee.
Diaz, Ottway, and Hendrick arrive at a river where Diaz, humbled by his journey and unable to walk, explains that he can accept dying in the middle of nature. Leaving Diaz to his fate, Ottway and Hendrick continue and are set upon by the wolves. Hendrick falls into the river and is trapped beneath the surface; Ottway is unable to pull him loose, and Hendrick drowns. Now alone, Ottway angrily appeals to God to "show him something real", but seeing nothing, decides he will “do it myself.”
Exhausted and suffering from hypothermia, Ottway eventually stops walking and goes through the collected wallets before arranging them into a cross. He realizes too late that he has stumbled right into the wolves' den – the team had been walking towards, not away from, the danger. Surrounded by the wolf pack and facing its leader, Ottway looks at his wife's photo in his wallet. It is revealed that she was dying of a terminal illness, the reason he was earlier preparing to kill himself. As the alpha wolf approaches, Ottway arms himself with a knife and shards of liquor bottles taped to his hand. He recites the words, "Once more into the fray. Into the last good fight I'll ever know. Live and die on this day. Live and die on this day." He charges the alpha wolf.
In a brief post-credits scene, the alpha wolf takes its last breaths, similar to the wolf Ottway shot and killed earlier. Ottway lies against the wolf, his fate unclear.