This is a gothic manga about a young man who embarks on a mystical journey to recover his 48 lost body parts taken by demons at birth.

Daigo Kagemitsu, a local lord with an ambition to rule the world, promises to give his new born boy's body to 48 demons in exchange for fulfilling his ambition. Accordingly, the baby boy comes to the world lacking 48 body parts, malformed, limbless and without facial features and internal organs and is thrown into the river.

Several years later, the boy named Hyakkimaru sets out on a journey to vanish demons to retrieve his lost body parts. Upon vanishing one demon, he retrieves one body part. Then, Hyakkimaru encounters Dororo, a sneak thief boy during his journey. Wherever they go, they are constantly attacked by demons.