Set in a world where animals speak, pray, and possess their own societies, the novel follows a half-breed wolf named Blacktail from his violent rise to power through an epic quest to awaken a sleeping deity known as the Forest God. Told almost entirely from animal perspectives, the story unfolds against a backdrop of ecological devastation in which humans have systematically destroyed forests, developed wild lands, and subjugated or exterminated wild creatures.
The novel opens with a lynx named Hate, whose childhood forest was demolished by human development and whose parents were killed by a car during their flight north. Now living in the shadow of a she-wolf named White-Eye who rules the mountain above, Hate learns that human hunters have killed White-Eye and three of her four pups. Hate stalks the surviving pup, but the pup is far larger and stronger than expected. In a prolonged fight, the pup breaks Hate's neck and marks the territory with a scent poem declaring himself Blacktail.
Two years later, Blacktail lives alone on his hill. He catches the scent of a female in heat and follows it into human territory, where he finds Renren, a large black dog chained in a backyard with no shelter. They mate, and Blacktail learns she is pregnant. Over the autumn he visits her nightly, urging her to come live on his hill, but she refuses out of fear, having never known freedom. When she finally agrees, her owner takes her to a veterinarian, where her unborn puppies are surgically removed. Blacktail returns to find Renren dead from internal bleeding. That night, he enters the house and kills the entire family. Half a world away, the Old Kitty Mother, an ancient house cat who leads a coven of lions in the Serengeti, senses Blacktail's act and is filled with joy, recognizing in him something she has sought for centuries.
A house cat sent by the Old Kitty Mother warns Blacktail that humans will raise an enormous hunt and he must flee south. Blacktail encounters a massive organized pursuit with hundreds of armed men, dogs, and helicopters. An elderly wild fox named Trap-Slipper, who encounters Blacktail by chance during the pursuit and offers his help, guides him through ditches, snowdrifts, and a terrifying cliff jump. When they are finally cornered, Slipper asks Blacktail to kill one man in honor of Slipper's mother, Snow, who died in a fur trap, then leaps from cover to draw the hounds away. The bloodhounds catch and kill Slipper, but one of them, recalling the Old Kitty Mother's curse on the murder house, pretends not to smell Blacktail's scent. Blacktail escapes south through neighborhoods, aided by house cats and dogs in the Old Kitty Mother's network.
In wild, mountainous territory, Blacktail meets the Old Kitty Mother herself, attended by two cougar bodyguards. She explains that the old animal gods have been destroyed by the god of men, but the Forest God, the god of the hunt, is not dead, only sleeping. Through a magical vision, she shows Blacktail the story of Karakaa, a holy crow who a thousand years ago bargained with a demon for the power to destroy European colonists on his lands. Karakaa succeeded, but the moon itself descended and he was never seen again, suggesting human dominion is protected by a force greater than mortal magic. Only the Forest God can break it. Reluctant but seeing human civilization spreading everywhere, Blacktail agrees to journey south and find Him.
The journey is brutal. Blacktail crosses mountains through winter, nearly starving, and begins experiencing dreams in which he inhabits the consciousness of suffering animals. Reaching a desert, he is clipped by a vehicle on an enormous highway, breaking his hind leg. A human serial killer who speaks the universal animal tongue finds him, nurses him back to health, and kidnaps a veterinarian to set the broken bone. In a cave lined with human skulls, a minor deity called the God of the Lost speaks through a dead body, telling Blacktail he will find what he seeks in "the Fire of God" (141), a phrase that later proves to refer to the archangel Uriel. Blacktail asks the god to protect his rescuer, and the god transforms the man into a coyote, freeing him from his human form.
Blacktail encounters Lord Fang's starving wolf pack, five wolves barely surviving on a mountain dominated by a grizzly bear called Fatberry. Blacktail is appalled to find that Little One, a half-breed runt, is forced to sleep alone. Blacktail, himself a half-breed, leaves the pack pile and sleeps beside Little One. In the fight against Fatberry, the bear kills Fang, but Little One fights on with desperate courage. Blacktail rises and kills the bear, then declares Little One the new pack lord.
Blacktail's journey grows dreamlike as he arrives at a small forest where domestic animals worship their human owner, a woman called Mercy. A renegade cat sorceress named Larkspur, a former apprentice of the Old Kitty Mother, reveals she transferred Mercy's terminal illness into Blacktail years earlier, meaning he is already dying. Blacktail attacks. He kills Sarge, Mercy's war-trained canine champion, who nearly disembowels him, and dispatches the remaining defenders, including biting off Larkspur's head. Inside the house, he wakes Mercy, expecting her to flee. She does, but returns with a wooden stick and smashes it over his head, then crouches over her wounded dog to shield him with her body. The sight triggers Blacktail's oldest memory: his mother shielding her puppies as she died. Unable to destroy the same love that defined his mother, Blacktail crashes through the wall and flees.
In the desert, Blacktail finds Chester, a half-breed dog abandoned by his owner and near death, and teaches him to hunt. A group of holy men build an enormous bonfire, and from the flames emerges the archangel Uriel, who offers Blacktail a peaceful afterlife with Renren's ghost and their restored puppies in exchange for abandoning his quest. Renren appears and confirms her love but furiously commands Blacktail to reject the offer. Blacktail walks into the fire and battles Uriel in a confrontation that expands to cosmic scale. He emerges wounded but alive. He sends Chester to find a mate and start a pack, then continues alone.
Blacktail arrives at a medical research facility where animals are infected with experimental diseases. Thousands of creatures line his path in silent reverence. He tears down the fences, frees every creature, and heals them with his own blood. Then he bites a researcher, who staggers out alive but infected. The blood curse Blacktail carries, a fusion of the experimental diseases from the facility, the illness Larkspur transferred into him, and his own divine blood, becomes unstoppable. The plague destroys human civilization. Only a handful of survivors remain: those who lived closely with animals and loved them. Their capacity for reason burns away, and they rejoin the natural order.
In the aftermath, the Old Kitty Mother, ancient and near death, encounters Chester, now a scarred pack king called Raze. He tells her of two dreams. In the first, Blacktail, now fully the Forest God, stood before Heaven's gates and summoned Karakaa, whose damnation was ended. Karakaa spoke a word that scattered the angelic armies, and Blacktail entered alone. The war between the Forest God and the god of men is over. In the second dream, Blacktail charged Chester with a message for the Old Kitty Mother: The violets grow also on his Far Hill, the animal afterlife, and the eye of hell is closed to her forever. The Old Kitty Mother, whose soul was stolen by a demon when she was a kitten, understands that Blacktail has freed her from damnation. She sets out to live whatever time remains, at peace.