It concerns a hero named Hyakkimaru, who has had much of his body stolen by forty-eight fiends, and has prosthetic replacements.

In exchange for "the power to bring back peace to the land", each of the fiends takes a body part from the baby, who is then abandoned by his father.

Hyakkimaru and Dororo come across a small, poor village full of people who are led by a woman named Mistress Yudai, who is actually a fiend who steals their money.

This ronin wields a sword known as Dragon Brood, which is possessed by one of the fiends that had stolen Hyakkimaru's body parts.

Hyakkimaru destroys the blade and regains his spine, overwhelming Misaki with grief for her brother in the process.

Hyakkimaru and Dororo travel to Daidara Mountain and arrive at a temple, where they meet Tahoumaru and Kagemitsu Daigo.

Tahoumaru helps Hyakkimaru defeat the fox, but threatens to kill him if he interferes with Daigo's plans.

Hyakkimaru, out of concern for Dororo's safety, dissolves their partnership and continues up a snowy path alone, killing demons as he goes.

After sneaking into the basement, Dororo discovers a cult of literally faceless individuals worshipping a Fiend called Legion, who has collected all their faces and uses their endless suffering to increase his power.

Along the way he is hounded by the distraught Misaki (from Chapter 2) who has still not forgiven Hyakkimaru for killing her brother, Tanosuke, and continues to attack him.

After Dororo and Hyakkimaru reunite and defeat the old man (the latter of which is another Fiend known as Redcap), they escape the mountain.

After passing through the demon-infested town and a cursed forest that causes wanderers to become lost, Hyakkimaru and Dororo come across the Gates of Hell.

They fight off a Fiend-possessed horse of Daigo's named Midoro before Hyakkimaru learns the truth about his curse.

Working their way through the traps, Dororo splits off to rescue the slave workers in the basement (as well as a reformed Tahoumaru, who has decided to help the duo) while Hyakkimaru goes on ahead and defeats more Fiends.

At the top of the tower, Hyakkimaru must fight his father after he is possessed by five Fiends at once, creating the monstrous Chimera.

Hyakkimaru defeats the Fiend straight after, recovers his arm and embraces the successfully exorcised Dororo.