Mizu seeks to avenge herself against the four European men present in Japan at the time of her birth (in secret defiance of Sakoku), one of whom may have been her rapist father, and another whom Mizu has already killed. She travels disguised as a man and encounters a "flesh-trader" (a purveyor of women to brothels) with a Western pistol in a ramen shop, whom she coerces into giving up the name of the weapons dealer, Heiji Shindo. Ringo, the kitchen attendant of the ramen shop, implores her to make him her apprentice.

Meanwhile, Princess Akemi, the only daughter of the Daimyo of Kyoto Lord Daiichi Tokunobu, tries to convince her father to approve of her marriage to Taigen, a young and accomplished Samurai of humble origins. Mizu arrives at the Shindo Dojo and requests a meeting with its master to procure the location of Heiji Shindo. When the request is denied she battles the better part of its students including their prized Samurai Taigen and wins before obtaining the information she requires and leaving Taigen dishonoured. The latter knew Mizu in their childhood as he and a group of children used to taunt and attack Mizu due to her mixed heritage appearance.

Reluctantly allowing Ringo to join her, Mizu arrives at a coastal town, seeking to hire a boat to reach Shindo’s island fortress. Shindo and the foreigner plot a 'surprise' for the Shogun in Edo. Taigen, having lost to Mizu, pursues her in order to regain his honor. As a result of Taigen's defeat, Akemi's father Lord Daiichi plans to marry her off to the Shogun's widowed second son and will take her to Edo in five days, despite her objections. She decides to run away in search of Taigen, although her father's retainer Seki catches her and, unable to stop her, joins her instead.

Upon Taigen's request, Ringo takes Mizu to a shrine where he attends to her. While she's regaining her strength Taigen draws up a contract for their next duel to which Mizu agrees. They are approached by a large man with a club, hired by Heiji. He delivers an invitation to a ‘Tea ceremony’. Though Taigen suspects this to be a trap, Mizu accepts and they both travel to meet Heiji in a secluded vale where Heiji gives Mizu three options: be paid off in return for her assurance that she'll renounce her vendetta, be smuggled into Heiji's castle in sake barrels to kill the white man, or refuse the first two options and be killed by archers supposedly hiding behind the cliffs. Mizu calls his bluff by refusing the offers, cuts off Heiji’s arm, and escapes the valley while being bombarded by scores of arrows. Afterwards Mizu knocks Taigen unconscious and leaves him with Chiaki's broken blade and a note promising to attend their duel at a later time. Taigen is subsequently kidnapped and taken to Heiji's castle.

Mizu seeks out Madame Kaji’s brothel to follow up on what Heiji Shindo revealed about how prostitutes enter the castle of Abijah Fowler, the white man she's seeking. At the brothel, Kaji promises to give her further information on how to access the castle if she agrees to mercy kill a young deaf-mute girl named Kinuyo who was in Kaji's care before being forcibly taken and presumably violated by the local thousand-claws mob boss Hamata. Mizu carries out her task without detection and leaves the scene making Kinuyo's death look like an accident, however on her way out a boy catches sight of her, and informs boss Hamata who arrives at Kaiji's brothel with his fighters and orders them to attack.

After realizing Akemi has run off, Lord Daiichi sends his men after her. Akemi’s search for Taigen eventually takes her to the same town as Mizu and upon seeing her admission to the brothel, Akemi persuades the purveyor to trade her there. To prove her competence when tasked by Madam Kaiji with pleasuring a veteran customer with erectile difficulties, she tactfully uses his interest in poetry and her proficiency in the subject to stimulate and bring him to climax. While she's being applauded for her talent she volunteers to serve Mizu in an attempt to drug her.

Faced with the threat of Hamata's men, Mizu gathers the women of the brothel in the cellar and tasks Ringo with guarding them. Inside the brothel she starts taking out the thousand-claws individually, but one manages to wound Mizu, resulting in her slowly losing strength.

In flashbacks, Mizu is seen receiving a similar wound from some gangsters, and is later saved by her presumed-dead mother, who goes on to arrange a marriage between Mizu and a disgraced Samurai, Mikio. Mizu gradually opens up to her new husband, but the relationship sours when Mikio hurts his pride when he loses a sparring match with Mizu, after which he calls her a “monster". A group of soldiers show up at their doorstep to collect the bounty on Mizu's head. Feeling betrayed by Mikio, she battles the group and kills them. Afterwards Mikio and Mizu’s mother fight over who tipped them off on Mizu’s whereabouts, leading to Mikio stabbing Mizu's mother to death. Mizu then kills Mikio and leaves.

A narrated bunraku puppet theater play intersperses and complements the storytelling, with its female protagonist eventually transforming into an Onryō, a vengeful spirit.

In the present, Mizu is pinned down but manages to summon back her strength, turns her sword into a makeshift Naginata and kills Hamata’s men. The men sent by Lord Daiichi arrive to take Akemi back home and though she pleads with Mizu to help her, Mizu doesn't intervene. Ringo, angered over his master's callous decision, ends his apprenticeship.

Mizu follows the instructions relayed by Madam Kaji, finding the underground passageway to the castle littered with the skeletons of women and infants. While trying to unlock the door to exit the tunnel, she accidentally triggers a water trap and just manages to escape drowning, but loses most of her gear. Her covert entrance is blown when a soldier sounds the alarm, interrupting Heiji and Fowler's meeting at the upper level with two of the Shogun's advisers as they conspire to kill the Shogun and his family to take power by force using guns in Fowler's possession.

Ringo saves Mizu and Taigen, bringing their unconscious bodies to Sword Father’s hut. While recovering, Mizu's relationship with Taigen starts taking a non-combative and suggestive turn, but soon comes undone when she reveals Akemi's marriage to the Shogun's family, and her withheld knowledge of Fowler's impending attack on the Shogunate. Taigen rejects Mizu's broken blade and leaves for Edo to save Akemi and warn the Shogun, vowing to kill her when he returns. After multiple failed attempts and an epiphany that results in mending ties with Ringo, Mizu manages to recreate the metallurgy of her sword's steel but refrains from reforging her sword until she has slain Fowler. Mizu and Ringo leave for Edo to save Akemi and kill Fowler.

Mizu asks Ringo to wait by the sewers while she saves Akemi and sends her his way. Taigen finds Ringo and they decide to storm the front gate to warn the Shogun about the impending attack, which shortly ensues as Fowler’s army breaks through the castle defenses. Seki saves Akemi from her cell, locking her father in her place, but they are out-numbered by soldiers until Mizu arrives. Heiji opens the final gate from the inside, giving Fowler access to the Shogun and his family. Fowler kills the Shogun, but the Shogun's sons and wife escape after Mizu crashes in, leaving Taigen to kill Heiji Shindo. Mizu subdues Fowler after starting a fire while attempting to stop him from fleeing, which rapidly spreads throughout the castle and then to the city.