The Ozunu Clan, led by the ruthless Lord Ozunu, trains orphans from around the world to become the ultimate ninja assassins. Raizo is one of the orphans. The Ozunu Clan's training is extremely brutal, especially for Raizo since he is to be the next successor of the clan. The only kindness he ever feels is from a young kunoichi named Kiriko, with whom he eventually develops a romantic bond. As time goes by, Kiriko becomes disenchanted with the Ozunu's routine and decides to abandon it. One rainy night, Kiriko climbs a wall to escape and encourages Raizo to join her, but he chooses to stay. Branded as a traitor, Kiriko is captured and later executed in front of Raizo by their elder ninja brother Takeshi, who impales her through the heart.
Years later, an adult Raizo is instructed by Lord Ozunu to complete his first assassination. After the mission, Raizo meets the rest of his clan atop a city skyscraper in Berlin. There, Lord Ozunu orders him to execute a kunoichi traitor. Remembering Kiriko's death, Raizo slashes Lord Ozunu's face with his kyoketsu-shoge and fights against his fellow ninjas. Barely surviving, he falls off the rooftop and into a river. After years, Raizo recovers and trains on his own to intervene in, and foil, all of Ozunu's assassination attempts.
Meanwhile, Europol agent Mika Coretti has been investigating money-linked political murders and finds out that they are possibly connected to the Ozunu. She defies her superior, Ryan Maslow, 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 Europol agents 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 ninjas infiltrate the Europol safe house, 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 execution. During the 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. He proceeds to kill Takeshi and confront Lord Ozunu in a sword duel. Mika interferes to help but gets 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 right side of her chest.
With the Ozunu defeated, Europol leaves. Raizo stays behind in the ruins of the Ozunu retreat. Climbing the same wall Kiriko did in the past, he looks out at the surrounding countryside with a smile, feeling his freedom for the first time.
