As a result of his selfish desires to rule the world, the powerful daimyo Daigo Kagemitsu sacrificed his infant son to 48 demons. The baby becomes malformed, limbless, and without organs as the demons descend upon him then scatter to create chaos in the world.
When sent adrift down the river, the infant is claimed by Dr. Junkai, who gives him new limbs as well as grafts a powerful blade to his left arm. With this sword of vengeance, the child is raised to hunt down the demons that took his body. This is the tale of that child that came to be known as Hyakkimaru, and his dangerous journey through the warring Sengoku period with the young Dororo, the greatest thief in Japan.