In the year 3048, the wounded Lord Kagemitsu Daigo proposes a deal to rule the whole world to forty-eight demons in their sealed temple. In return, the demons ask forty-eight parts of the body of his unborn son. When the mutilated baby is born, his mother puts him in a basket in the river flow to save his life. The baby survives and becomes the demon slayer Hyakkimaru that slash demons to retrieve his body parts. During his journey, he meets the female thief Dororo, who was raised as a boy after the death of her parents by the evil Lord Daigo, in a small town and she befriends Hyakkimaru and joins him in his quest seeking revenge against the Daigo's clan.