In a time when the great war between five rival races for supremacy on Earth ended with humanity's victory led by the hero Sid, the world suddenly gets "overwritten" right before the eyes of a boy named Kai. In this rewritten world, Kai witnesses humanity's defeat in the war as a result of Sid's absence—where dragons and demons now rule the land, and Kai himself has become a forgotten existence to all humans. However, after encountering the mysterious girl Rinne, Kai resolves to break free from this rewritten fate. In a world without a hero, he inherits the sword and martial skills of the hero (Sid) and challenges the powerful enemy races that dominate the land.

The world as we know it is actually just half the story, as Takeshi Nanase finds out abruptly one summer morning. On his way to kendo practice, Takeshi comes across an unconscious girl in a uniform he doesn't recognize. Takeshi does the decent thing and saves her, and in return the girl wakes up and accidentally turns him into a magic-user. As Takeshi finds out, there is the world he lives in and the world of magic users. Most magic users just want to peacefully coexist with non-magicians, but there are some with bigger ambitions. Mui Aiba is a magician enrolled in the Subaru Magic Academy, where magic users can learn to control and channel their powers and how to live in peace with regular humans. After his fateful encounter with Mui, Takeshi and his newly magician friends Kurumi Isoshima and Kazumi Ida decide to enroll in the Magic Academy as well. All three friends have different reasons for fighting on, whether they're fighting to escape the past or catch up to the future. They wield different kinds of powers, which they must learn to harness in order to fight off the Ghost Trailers, a group of magicians who are willing to use violence to assert their superiority over humans. Pursued by the Ghost Trailers, Takeshi and his friends must train to become stronger, face the leader of the Trailers, and prevent the beginning of the Second Great Magic War.

In the light of day and in the dead of night, mysterious horrors await in the darkest shadows of every corner. They are unexplainable, inescapable, and undefeatable. Be prepared, or you may become their next victim. Sit back in terror as traumatizing tales of unparalleled terror unfold. Tales, such as that of a cursed jade carving that opens holes all over its victims' bodies; deep nightmares that span decades; an attractive spirit at a misty crossroad that grants cursed advice; and a slug that grows inside a girl's mouth. Tread carefully, for the horrifying supernatural tales of the Itou Junji: Collection are not for the faint of heart.

The world is divided into two kingdoms: the Kingdom of White, which floats in the heavens and is ruled by their queen Iris, and the Kingdom of Black, which stands upon desolate land below and houses the King of Darkness as its ruler. As of late, forces of evil have amassed great power, posing a threat to the entire world. Being the main representative of the Light, it is Iris' duty to maintain the balance of the world and fight off the darkness in her kingdom. Meanwhile in the Kingdom of Black, rampaging monsters annihilate a certain boy's village, leaving him the sole survivor. As he grieves in hopelessness, an armored man named Skeer notices the child and comforts him. Soon after, Skeer recognizes the boy's potential to change the kingdom's status quo and makes him his heir before passing away. The boy then vows to become the Prince of Darkness—the one who will replace the King—to bring the world back to its rightful path. As Iris and Prince of Darkness each challenge the impending doom the world faces in their own respective ways, their destinies will converge with each other, and perhaps, their bond will decide the fate of the world. [Written by MAL Rewrite]