A team of Koga Ninja is sent to investigate a plague in Shimoda village, but on their way they are slaughtered; the only survivor is Kagero, a beautiful Kunoichi who is their lord's poison-taster. Their assailant is a giant man named Tsai, a killer with stone skin, and a colossal double-bladed sword, which can be thrown like a boomerang. Kagero attempts to escape, but the giant uses his weapon to cut off the branch she jumps onto, making her fall into his hands unconscious.
The giant takes Kagero to his hut and proceeds to rape her, but he is interrupted by an interloper who is not intimidated by his ability to turn his skin into stone. The interloper, a ninja vagabond named Jubei Kibagami, blinds one of his eyes with a dart and escapes with Kagero.
Although Tsai has the clear advantage in his pursuit, as Jubei cannot even scratch his stony hide, he begins to fall apart due to the poison received from raping Kagero. The giant throws his sword, but he cannot catch it when Jubei manages to cut his fingers off; the blade drives into the giant's skull, killing him. An old monk who witnessed the battle congratulates Jubei, but he remarks that although Jubei's triumph over the demonic warrior was impressive, he had outside help. He calls the monster one and the first of "the Eight Devils of Kimon."
Several other strange characters are concerned with the stone man's death: The well-dressed man Yurimaru, who calls the giant Tessai, and the scarred, explosive-wielding female Zakuro, who lusts for Yurimaru, even though Yurimaru is gay (or Shudo) and sleeping with their master, Gemma.
Jubei rests in a hot spring, but is entranced by a female bather and her snake tattoos. She identifies him as the man who killed Tessai, and her tattoos begin to move. This hypnotizes Jubei, and the snakes leave her body and approach him. A shuriken strikes Jubei, which wakes him in time to cut the snakes down. He grabs the woman, but she sheds her skin and escapes. The old monk appears again; Jubei learns his name is Dakuan, and the shuriken was poisoned. Jubei must work for Dakuan, a Tokugawa Shogunate operative, in order to receive the antidote, or he will surely die within two days.
As they boat down a river, Dakuan asks Jubei if he killed the chief retainers to the Yamashiro clan five years before, and leader of the Yamashiro ninja, Himuro Gemma, who were getting rich off a hidden and undisclosed gold mine. Dakuan claims that Gemma is still alive, despite Jubei's insistence to the contrary; a flashback reveals that Jubei did indeed kill his comrades in the Yamashiro clan in self defense after they were ordered by Gemma to kill him. As revenge, Jubei ambushed Gemma and cut off his head.
After landing, they are separated. A shadow attacks Dakuan with a mechanical claw, apparently impaling him against a tree, but the old monk escaped into the branches, camouflaging himself. A man rises out of the shadow, musing that nobody could escape "Shijima's claw," and then depart.
Jubei enters an abandoned shrine, where an old woman is chanting the sutra for the dead of Shimoda. She turns out to be a trap and is cut in half by Jubei (revealing that she was full of snakes), and the woman from the spring, Benisato, returns. Kagero grabs Benisato from behind and puts her knife to her throat. A snake slithers out of Benisato's vagina and bites Kagero, but she does not relent. Benisato suddenly dies of electrocution. A thin metal wire, glowing white hot, stretches for miles, and at the other end Yurimaru admonishes Benisato for her failure and disintegrates the wire before Jubei and Kagero can locate its source.
When Jubei tries to suck the poison from Kagero's wound, she kicks him away, telling him that she is immune. Dakuan returns and requests that Kagero join them in their fight against the common enemy, and claims he has valuable information: He tells Jubei that Kagero poisons any man she sleeps with, and that's how Jubei was able to defeat Tessai.
Meanwhile, Yurimaru, Zakuro, and two other Devils gather to figure out how to defeat the man who killed Tessai.
Jubei and Kagero go with Dakuan to Shimoda, where they see the well had been poisoned. A swarm of wasps descends on the village, going after the three of them. Kagero holds them off, and Jubei finds the master of the swarm, a hunchback named Mushizo, another of the Eight Devils, who lets slip that Gemma is still alive. The hunchback's hump is actually a wasp nest growing from his back, and the wasps attack Jubei. They fight in a water-powered mill, and then Jubei escapes into the river. Mushizo follows him, but remains on land. Jubei knocks him into the water, where the wasps sting Mushizo repeatedly in trying to escape, distracting him long enough for Jubei to kill him with his sword.
Danzan, Kagero and Jubei climb a cliff to get a better view of the land, but Kagero sees her former commander, Hanza (whose arms Tessai had torn from their sockets), walking aimlessly toward the brink. His eyes and mouth have been sewn shut. Kagero stops him, but Zakuro is there, and she releases streams of gunpowder into the air. Hanza reacts with it, and explodes. Jubei grabs Kagero and throws himself off the cliff to save her.
Jubei is hanging by the cord attached to his sword sheath, and he has Kagero climb up the cliff. When Jubei gets there, a swordsman in white is holding his sword. He introduces himself as Utsutsu Mujuro, and challenges Jubei. Jubei lures the swordsman into a nearby bamboo forest, hoping to take advantage of his blindness, but Mujuro's ears are sharp. Mujuro proves himself more than a match for Jubei. As Mujuro attacks, Jubei is barely able to deflect Mujuro's blows. Kagero tries to attack Mujuro from behind, but is unsuccessful, and her blade gets stuck in a bamboo tree. Mujuro then blinds Jubei with the reflection off his katana blade. It is only by sheer luck alone that Mujuro's killing blow is blocked by Kagero's blade. Jubei then impales Mujuro.
Jubei accuses Kagero of not valuing her life, and she responds by saying that she cannot touch a man, lest she kill him. Kagero passes out through fatigue, and awakens with Jubei. He notices a beached cargo ship, and concludes that the Devils poisoned Shimoda to keep it secret, so they could take the cargo. Kagero wants to stop the cargo from reaching Kishima Harbour, where it will be taken away by boat, so she agrees to work with Jubei until then.
Dakuan finds them, and tells them that the cargo is the gold from the secret Yamashiro mine, which the Shogun of the Dark will use to topple the Tokugawa and initiate a civil war. Jubei chases after something that has followed him, and Kagero sends a message to the chamberlain. She then demands that Dakuan give her the antidote for Jubei. He tells her the secret of the antidote, and it shocks her.
Jubei returns from the chase that yielded nothing to find Kagero kidnapped, and a ransom note carved into a tree. Dakuan tries to dissuade him, but he runs off after her. He finds her in an abandoned building, but when she awakens, she attacks him, with a disembodied voice goading her on. Jubei has to allow Kagero to stab his wrist so he can block the incoming spring-loaded claw from the shadow. He throws his sword toward the shadow, and he impales Shijima in the back. Kagero snaps out of her trance with her captor's death.
Two hours later, the Koga army hasn't arrived, and Kagero wonders why Jubei stepped into an obvious trap to save her. He tells her that she's his comrade, as they've worked together since the day before. Kagero then tells him that she has to pay back the debt garnered when Jubei saved her, and insists that she do so now. She strips, and tells him the antidote for his poison is another poison: She can save him, if he sleeps with her. He refuses, and departs to intercept the Shogun of the Dark's forces, leaving Kagero in tears.
Jubei meets up with Dakuan, and plans to sink the ship when it's fully loaded and out to sea. The Mochizuki have apparently decided to intervene, but the chamberlain stabs Kagero, and transforms into Gemma. Jubei attacks, slaughtering the ninja horde that stands in his way. Yurimaru asks for the honour of killing Jubei, and Gemma lets him.
Yurimaru leads Jubei into a warehouse, where he strings him up and electrocutes him. Yurimaru notices a rat scurrying about, and then it collapses. He sees the sutured cut on its belly, and the gunpowder on the ground, and then the rat explodes. Yurimaru's dismembered arm falls into the water, and Zakuro picks it up. She muses that he "accidentally" walked into her trap, and now he's "Queen of the Devils."
Jubei finds the dying Kagero, who is glad that she found someone who treated her as a person, and not an expendable soldier. She expresses her wish that they could have made love just once, and they kiss just before she dies, curing Jubei. Setting her adrift on a funeral boat, Jubei takes her headband and tears the arms off his shirt.
Gemma meets the leader of the Toyotomi ninja, and declares that the Devils of Kimon (of which only two remain at this point, himself and Zakuro) will take the gold and build a ninja army to terrorize Japan, and not even the Shogun of the Dark can stop them.
Zakuro finds Dakuan rooting about in the hold, and he throws one of his gourds at her. She cuts it in half, spraying liquid on her and the floor. Dakuan grabs a candle, but she puts it out. Jubei appears with another lit candle, and ignites the flammable oil, immolating Zakuro. Her gunpowder also explodes, breaching the hull and setting alight the ship's interior.
Gemma enters the hold and finds Jubei, and they fight to the death. Jubei cuts Gemma's arm off, but Gemma still manages to throw Jubei a beating before reattaching it. The fight is brutal, but even when the ceiling crashes down on him, Gemma keeps going while impaled on a wooden beam. Jubei stabs him and cuts upward, splitting him in half from the belly up. Gemma again recovers, but a river of molten gold flows over him. Gemma grabs onto Jubei climbing to safety, but Jubei slices off his left arm in one swift cut at the last second while delivering the iconic line, "Gemma, burn in your golden hell!" The villain falls into the molten metal, sinking to the bottom of the sea as a statue.
In the epilogue, Dakuan congratulates himself for such masterful manipulation of Jubei and Kagero. Angry at being used, Jubei sends the gold Dakuan is holding (including his cut, one hundred gold pieces) into the sea and tells the old man to stay away from him. He jumps into the water, and is last seen walking into a fog, with Kagero's headband tied around the sheath of his sword.
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