In Japan's Warring States period, Lord Daigo Kagemitsu makes a pact with 12 demons, offering them his unborn son in exchange for the prosperity of his lands. Years later, young thief Dororo is attacked by a ghoul but rescued by a mysterious boy, whose body parts turn out to be almost entirely prosthetic.

Dororo and Hyakkimaru happen upon a village and are brought before its chief, Lady Bandai. However, Hyakkimaru inexplicably draws his sword in her presence, resulting in both him and Dororo being locked in a storehouse by the villagers. It turns out they are not the only ones confined there...

Jukai is a doctor who travels the land fitting prosthetic arms and legs to those who have lost their limbs in war. One day, on the riverbank he finds a baby missing most of its body parts. He decides to raise the child, who he names “Hyakkimaru”. Jukai provides the child with prostheses, but the time comes when Hyakkimaru sets out on a journey to recover his own body parts.

Dororo Onikimaru confronts Tanosuke, a manly slaughter. The sword he wields was a cursed decoy where the devil lives. Although barely dismissing Tanosuke, the military sword has passed over to the hands of the hands and the horsemans are manipulated by the weapon.

Struggling to adapt to an unfamiliar world of "sound", Hyakkimaru is injured in a fight with a ghoul. He is taken in and nursed by a girl named Mio, who looks after children orphaned by war. However, after becoming aware of a demon nearby, Hyakkimaru heads out to fight it before he is fully recovered.

Hyakkimaru has regained his voice from the devil god, but one leg was stolen from him. After returning to the deserted temple and having his wounds taken care of, he again goes into battle with the demon. Meanwhile, in the abandoned temple where Mio and the children are waiting ...