To secure his rule over Japan, the tyrannical lord Daigo Kagemitsu sacrifices his unborn child to 48 demons. The pact is sealed, and the infant is born without limbs, only to be abandoned in a raging river. Fifteen years later, a resourceful orphan named Dororo fights to survive in a war-ravaged land, battling starvation and hostile samurai. After provoking a gang of thugs, Dororo is cornered until a masked stranger intervenes, claiming to sense nearby spirits. A river monster soon appears, and the stranger reveals prosthetic arms containing hidden blades, using them to defeat the beast before disappearing. Intrigued, Dororo tracks the man down and insists on joining him. The stranger, Hyakkimaru, explains that the demons stole his body parts and that he is hunting them to reclaim his humanity. Despite his isolation, Dororo refuses to leave his side. Together, they journey across a brutal Japan, accompanied by a dog named Nota, confronting the horrors of both the spirit world and human cruelty.