In a civilized society of anthropomorphic animals, an uneasy tension exists between carnivores and herbivores. At Cherryton Academy, this mutual distrust peaks after a predation incident results in the death of Tem, an alpaca in the school's drama club. Tem's friend Legoshi, a grey wolf in the stage crew, has been an object of fear and suspicion for his whole life. In the immediate aftermath of the tragedy, he continues to lay low and hide his menacing traits, much to the disapproval of Louis, a red deer and the domineering star actor of the drama club. When Louis sneaks into the auditorium to train Tem's replacement for an upcoming play, he assigns Legoshi to lookout duty. That very night, Legoshi has a fateful encounter with Haru, a white dwarf rabbit scorned by her peers. His growing feelings for Haru, complicated by his predatory instincts, force him to confront his own true nature, the circumstances surrounding the death of his friend, and the undercurrent of violence plaguing the world around him.

Mysterious immortal humans known as Ajin first appeared 17 years ago in Africa. Upon their discovery, they were labeled as a threat to mankind, as they might use their powers for evil and were incapable of being destroyed. Since then, whenever an Ajin is found within society, they are to be arrested and taken into custody immediately. Studying hard to become a doctor, Kei Nagai is a high schooler who knows very little about Ajin, only having seen them appear in the news every now and then. Students are taught that these creatures are not considered to be human, but Kei doesn't pay much attention in class. As a result, his perilously little grasp on this subject proves to be completely irrelevant when he survives an accident that was supposed to claim his life, signaling his rebirth as an Ajin and the start of his days of torment. However, as he finds himself alone on the run from the entire world, Kei soon realizes that more of his species may be a lot closer than he thinks.

Hole—a dark, decrepit, and disorderly district where the strong prey on the weak and death is an ordinary occurrence—is all but befitting of the name given to it. A realm separated from law and ethics, it is a testing ground to the magic users who dominate it. As a race occupying the highest rungs of their society, the magic users think of the denizens of Hole as no more than insects. Murdered, mutilated, and made experiments without a second thought, the powerless Hole dwellers litter the halls of Hole's hospital on a daily basis. Possessing free access to and from the cesspool, and with little challenge to their authority, the magic users appear indomitable to most—aside for a few. Caiman, more reptile than man, is one such individual. He hunts them on a heedless quest for answers with only a trusted pair of bayonets and his immunity to magic. Cursed by his appearance and tormented by nightmares, magic users are his only clue to restoring his life to normal. With his biggest obstacle being his stomach, his female companion Nikaidou, who runs the restaurant Hungry Bug, is his greatest ally.

The year is 2071. Humanity has been pushed to the brink of extinction following the emergence of man-eating monsters called Aragami that boast an immunity to conventional weaponry. They ravaged the land, consuming almost everything in their path and leaving nothing in their wake. To combat them, an organization named Fenrir was formed as a last-ditch effort to save humanity through the use of God Eaters—special humans infused with Oracle cells, allowing them to wield the God Arc, the only known weapon capable of killing an Aragami. One such God Eater is Lenka Utsugi, a New-Type whose God Arc takes the form of both blade and gun. Now, as one of Fenrir's greatest weapons, Lenka must master his God Arc if he is to fulfill his desire of wiping out the Aragami once and for all. The monsters continue to be born en masse while the remnants of humanity struggle to survive the night. Only God Eaters stand between the Aragami and complete and total annihilation of the human race.