In the final chapter of the novel, Buck begins hearing the call of the wild, which is his inherent primitive nature beckoning him to the wilderness, where his ancestors roamed freely as wolves. Despite his affection for John Thorton, Buck begins spending days at a time away from camp and roams the wilderness like a wolf in search of food. In the wilderness, Buck hunts and eats salmon out of the river. Buck also kills a bear and takes down a moose, revealing his violent instincts and impressive strength. In the wilderness, Buck is completely in tune with his ancestral spirit and behaves like a wolf as he stalks his prey. Tragically, Buck returns to camp one day to discover that John Thorton and his friends were violently murdered by a tribe of Indians. In a fit of rage, Buck avenges John's death by viciously slaughtering the remaining Indians.

As the title suggests, Buck answers the "call of the wild" and returns to his atavistic state. That is, he behaves more and more like a wolf. Buck becomes the head of a pack, and in the pale moonlight, he can be seen with his "great throat a-bellow as he sings a song of the younger world, which is the song of the pack."

After being nursed back to health by John Thornton, Buck saves the man's life twice. But, because Thornton and the others have gone to Eastern Alaska to seek gold, Buck and the other sled dogs have led existences that are different from others. Much like wolves, they have "feasted riotously" at times; at other times, they have gone hungry. Sometimes, Buck lies by the fire, and he has memories of spending a night under a tree where a hairy man was settled. In connection with this hairy man is a call Buck hears away in the trees. It is a call from the wild dogs of the forest.

It caused him to feel a vague, sweet gladness and he was aware of wild yearnings and stirrings from he knew not what....Irresistible impulses seized him....He began to sleep out at night, staying away from the camp days at a time. (VII)

More and more Buck breaks away from civilization. For four days he watches an old bull moose, and when it is weakened from lack of water and the chance to graze, Buck kills it. Later, on his return to camp, Buck sees one of the dogs writhing in pain as it dies. He senses that something is wrong. Crawling on his belly, Buck watches the Yeehats' celebration. Then, he "hurled himself upon them in a frenzy to destroy." The Indians flee in a panic, sure that they are fleeing the Evil Spirit. Buck is no longer afraid of men because he realizes how easily he defeats them if they have no weapons in their hands.

After this defeat of the Indians, Buck enters the wild and joins the pack in which an old wolf with whom he once ran came up to him. The old wolf sat down and howled. Buck howled. Then as the other wolves fell in, Buck ran with them. But every year Buck returns to a certain valley. Sometimes he is alone. At other times, he has a pack that follows him, and he bellows the sound of the pack.