In a bid to strengthen his rule over Japan, the merciless lord Daigo Kagemitsu strikes a deal with 48 demons to sacrifice his unborn child. When the child is born disfigured and abandoned, fifteen years pass before a feisty youth named Dororo fights for survival in a destitute and war-torn village. After a confrontation with thugs, a stranger with extraordinary abilities saves Dororo from a river monster, revealing a tragic past where demons took his limbs. Despite warnings, Dororo insists on joining this enigmatic man, Hyakkimaru, on a quest across Japan, facing both demonic foes and human cruelties alongside a loyal puppy named Nota.