The Ozunu Clan, led by the ruthless Lord Ozunu (Sho Kosugi), trains orphans from around the world to become the ultimate ninja assassins. One of these orphans, Raizo (Rain), was forced to train as an assassin for the clan. The training was both brutal and hard especially for him because he was to be the next successor of the clan. The only kindness he was ever shown was from a young kunoichi named Kiriko, with whom he eventually develops a romantic bond. As time goes on, Kiriko becomes disenchanted with the Ozunu’s routine and wishes to abandon it for freedom. One rainy night, Kiriko decides to make her escape and encourages Raizo to join her; however he decides to stay. Branded as a traitor, Kiriko was caught and later executed in front of Raizo by their elder ninja brother Takeshi, impaling her through the heart. As a result of Kiriko’s death, Raizo begins to harbor resentment and doubt towards the Ozunu. Kiriko’s death opens his eyes and he begins to see faults within the clan and sees that what he’s been taught to do wasn’t right. Some time later, Raizo is instructed by Lord Ozunu to complete his first assassination. Afterwards, Raizo meets the rest of his clan atop a city skyscraper in Berlin. There he is instructed by Lord Ozunu to execute another kunoichi traitor like Kiriko. Upon remembering Kiriko’s death and finally having had enough, Raizo cracks. He rebels against Lord Ozunu by cutting his face with a kyoketsu-shoge and engages in combat against his fellow ninja kin. Barely surviving, he falls off the roof of the skyscraper and into a river. For the years that are to come, Raizo recovers and trains on his own to intervene and foil all of Ozunu’s assassination attempts in hopes of bringing down the clan that took everything from him.
Meanwhile, Europol agent Mika Coretti (Naomie Harris) has been investigating money-linked political murders and finds out that they are possibly connected to the Ozunu. She defies her superior, Ryan Maslow (Ben Miles), and retrieves secret agency files to find out more about the investigation. Mika meets Raizo and convinces him to see Maslow for protection as well as to provide evidence against the Ozunu. However, Raizo is arrested by Maslow and abducted by agents from Europol for interrogation. Although feeling betrayed, Mika is assured by Maslow that he is still on her side and gives her a tracking device for emergencies. The Ozunu ninja infiltrate the Europol safehouse where Raizo is being held in an attempt to kill him and everybody inside. Mika frees Raizo and they both manage to escape, but Raizo suffers near-fatal wounds. Mika then takes him to a motel to hide. Resting in the motel, Mika implants the tracking device into Raizo, as the ninjas remain in pursuit. Unable to fend off the Ozunu, she hides outside the motel until Special Forces arrive to help her.
By the time they arrive, the ninjas have already kidnapped Raizo, bringing him before Lord Ozunu for prosecution. During transport back to the Ozunu, Raizo uses his ninja techniques to heal his own wounds. Europol special forces and tactical teams led by Maslow storm the secluded Ozunu retreat (nestled in the mountains) using the tracking device on Raizo. Turning the night into day by saturating the sky above with powerful flares, the military forces are able to fight the ninjas on their own terms. In the confusion, Mika frees Raizo from his bindings, where he proceeds to kill Takeshi and confront Lord Ozunu in a sword duel. Mika interferes to help, but is stabbed by Lord Ozunu. Enraged, Raizo uses a ‘shadow blending’ technique for the first time to distract and kill Lord Ozunu. Mika, seemingly fatally wounded, is in fact saved by a quirk of birth: her heart is actually on the opposite side of her chest. After Europol leaves, Raizo stays behind to tend to the ruins of the Ozunu retreat. He later climbs the same wall Kiriko did while trying to escape in the past, and looks out at the surrounding countryside, recognizing his freedom for the first time.