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.

Meg, faithful and gentle, Jo, independent and energetic, Beth, quiet and shy, Amy, amiable and precocious–the four sisters live vigorously and happily at home with their gentle mother while waiting for their father to return from the Civil War. Helping each other, they challenge their fates and grow up to become wonderful women.

Individuals who can materialize weapons from their soul are called Blazers, and they attend Kouryou Academy High School in order to harness their abilities. Each student is required to partner with another, in the hopes that one day, the pair can attain the power of Absolute Duo. Tooru Kokonoe hopes to attend this academy in order to gain power after his sister and friends were slain by a mysterious man. However, at the opening ceremony, he is forced to duel against the person sitting next to him, with the loser being expelled. As Tooru prepares to give the match his all, it is not a weapon that manifests from his soul, but a shield, an irregularity which catches the attention of a foreign student named Julie Sigtuna.

As spring vacation comes to a close, a new school semester approaches. Deciding to make the most of the remaining holiday, Ayuko Uehara takes a stroll into her neighborhood and stops by a small cafe. However, her peaceful day is abruptly disturbed when a girl clumsily bumps into her. Left puzzled by the encounter, Ayaku is even more surprised when she meets them again as freshmen at the same high school she attends. Recognizing her from the store, the girls introduce themselves as Kanaka Amaya and Saki Iwasawa, and the three quickly become friends. As they go through their daily lives as high school girls, the trio's distinct personalities—Kanaka's happy-go-lucky attitude, Saki's tomboyish behavior, and Ayuko's easygoingness—are sure to make every mundane school day filled with silly and fun interactions.