Feudal Japan during the Edo period is the setting for a conspiracy that threatens to overthrow the Tokugawa Shogunate. The Yamashiro clan secretly mines gold and ships it to the Toyotomi Shogun of the Dark, who intends to use the wealth to purchase advanced Spanish weaponry and seize power. When the gold-laden ship runs aground in a storm on Mochizuki territory, the Eight Devils of Kimon, a team of ninjas with supernatural abilities employed by the Yamashiro, massacre the nearby village of Shimoda to keep the shipment hidden. While investigating the deaths, a Mochizuki Koga ninja team is slaughtered by the Devils. The sole survivor, a kunoichi named Kagero, is captured by one of the Devils, the stone-skinned Tessai, who attempts to assault her.

Kagero is rescued by Kibagami Jubei, a mercenary swordsman and former Yamashiro ninja who now wanders as a ronin. Jubei kills Tessai, but soon finds himself blackmailed by Dakuan, a cunning spy for the Tokugawa government. Dakuan stabs Jubei with a poisoned shuriken and promises an antidote only if Jubei helps eliminate the remaining Devils. Jubei learns that the leader of the Devils is Himuro Gemma, his former commander, who five years earlier had ordered his own ninja team to kill each other to conceal the gold mine's location. Jubei had survived that betrayal and decapitated Gemma in revenge, but Gemma survived due to his immortality and now seeks to complete the conspiracy.

Kagero, whose body is infused with deadly toxins that kill anyone who becomes intimate with her, agrees to join Jubei and Dakuan. The trio discovers that the villagers of Shimoda were killed by poisoned water, made to look like a plague. They are attacked by three more Devils: Mushizo, who controls a swarm of bees from a tumor on his back; Zakuro, a master of explosives; and Utsutsu Mujuro, a blind swordsman with superhuman hearing. Jubei kills Mushizo and Utsutsu, while Zakuro escapes. Following the trail, Kagero deduces the gold has been moved to Kashima Harbor for transfer to the Shogun of the Dark's ship.

At Kashima, Jubei battles Shijima, a Devil who can control shadows and hypnotize others. Kagero sends word to the Mochizuki chamberlain Sakaki Hyobu to bring his army. Dakuan reveals that the only cure for Jubei's poison is to copulate with Kagero, as her toxins would neutralize his. When she offers herself, Jubei refuses, prioritizing stopping the gold shipment. Kagero goes to meet Sakaki, but he stabs her, revealing himself to be Gemma in disguise, having murdered the real chamberlain. Enraged, Jubei fights through waves of enemies and is nearly killed by Yurimaru, Gemma's right-hand and a Devil who can electrify threads and turn invisible. A gunpowder-rigged rat left by Zakuro as a trap for Yurimaru kills the Devil, allowing Jubei to escape. He finds Kagero mortally wounded; she confesses her love and they kiss, curing Jubei's poisoning before she dies, giving him her headband as a keepsake.

Jubei and Dakuan board the departing ship. Onboard, Gemma kills the Shogun of the Dark's envoy, revealing his true plan to use the gold to raise his own ninja army and terrorize Japan rather than serve the Toyotomi. Jubei and Dakuan set the ship ablaze in a confrontation with Zakuro. In a brutal final battle, Jubei fights Gemma as the gold melts from the heat, engulfing the immortal leader and sinking him to the bottom of the sea. Dakuan thanks Jubei for his humanity, and Jubei resumes his solitary wandering, now carrying Kagero's headband tied to his sword's hilt.