时为战国。醍醐之国主景光,在某所寺院的大堂中,向12尊鬼神像许愿领土繁荣。作为交换而诞生的景光之后嗣,身体各处都有所欠缺,被视作不祥之子而抛弃到河川之中。时光流逝,鬼神实现了与景光的约定,国家迎来了平安。这样的某天,名为“多罗罗”的年幼盗贼,与某个男人相遇。 那是鬼,还是人——两臂装有刀剑,全身皆为人造的男人“百鬼丸”,其无光之瞳紧紧盯着袭来的妖魔。Daigo Kagemitsu, who works for a Samurai general in Japan's Warring States period, promises to offer body parts of his unborn baby to 48 demons in exchange for complete domination of the country. When the baby boy is born, Daigo has him thrown into a river, expecting the boy to die. A kind sage, however, finds him and adopts him. The sage fits out his poor son with prosthetics. Time goes by and the baby grows into a boy who calls himself Hyakkimaru. Every time Hyakkimaru eliminates a demon, he retrieves one of his body parts. Hyakkimaru rescues a boy thief named Dororo from a band of men whom the young boy tried to rob. Together they travel the countryside in search of the demons who possess Hyakkimaru's parts. Throughout their travels, they face a host of monsters and ghosts.