In an effort to strengthen his grip on Japan, the ruthless lord Daigo Kagemitsu makes a dark deal with 48 demons, sacrificing his unborn child in the process. The child is born limbless and cast into a tumultuous river. Fifteen years later, Dororo, an orphan who has learned to fend for himself in a devastated land plagued by war, struggles against hunger and the dangers posed by rival samurai. When Dororo incites a group of violent thugs, he finds himself trapped, only to be rescued by a mysterious figure in a mask, who claims to detect nearby spirits. Shortly after, a monstrous creature emerges from the river, and the stranger unveils prosthetic arms equipped with concealed blades, which they use to vanquish the beast before vanishing into the night. Curious, Dororo follows the masked individual and demands to join their cause. The stranger, identified as Hyakkimaru, discloses that the demons have stolen his body parts and he is now on a quest to retrieve them and reclaim his body. Despite Hyakkimaru's preference for solitude, Dororo persists in accompanying him. As they travel through Japan, battling the terrors of the spirit realm and the harsh realities of human wickedness, they are joined by a dog called Nota.
