In a time when nearly all dogs have been euthanized as a safety precaution, fifth-grader Ashley Dubois and her friend Mason discover a book that claims something unbelievable—that people and dogs once lived happily together. They seek a mad scientist named Dr. Bukowski to discover the truth.

Meanwhile, Amy-Bell, a Great Dane mix, is separated from her owners during a round-up of the few remaining dogs. As the reluctant leader of a small group of dogs who escaped, Amy-Bell tries to care for them.

When Ashley and Mason find Dr. Bukowski and his pack of renegade dogs, they’re shocked to find the animals aren’t vicious killers. So they join the quest to save the last dogs—Amy-Bell and her pack—before it’s too late.