Hyakkimaru is boy befallen and surrounded by tragedy. Before he was born, his father Daigo aspires to rule Japan and does so by making a pact with 48 majin.

His side of the bargain? 48 of the body parts of his soon-to-be born son. Hyakkimaru, now a disfigured and horrid looking infant that can no longer be called human, is cast away by his family.

Years later, Hyakkimaru, now a young man, makes it his life goal to hunt down the 48 majin and restore his body parts, having already gained some by the time we see him.

Along this journey, he comes across a brat in danger who goes by Dororo. After being rescued, Dororo becomes a pest that Hyakkimaru can't seem to shake.

With Dororo's cunning, and Hyakkimaru's wit, the two head off into a long and perilous journey.