Lore

During the Battle of Okehazama, Samanosuke of the Akechi clan watches but is attacked by Imagawa Yoshimoto's men. Though Nobunaga Oda was victorious against Yoshimoto, he is fatally wounded and assumed dead. A year later, Samanosuke receives a letter from his cousin Princess Yuki of the Saitō clan for his assistance as she fears monsters are behind the disappearances of her servants. Joined by Kaede, Samanosuke arrives too late to Inabayama Castle as Yuki is abducted as he and Kaede split up to cover ground. After being defeated by a monster while trying to rescue Yuki, Samanosuke is visited by the twelve oni who give Samanosuke the power to vanquish the monsters that abducted Yuki, the Genma, and seal their souls in a mystical gauntlet. While searching for Yuki, Samanosuke finds a laboratory and encounters the Genma scientist Guildenstern, learning that the Genma have resurrected Nobunaga to serve them before slaying Guildenstern's creation Reynaldo. Samanosuke later encounters Nobunaga's servant Tokichiro as he attempts to recruit him before being reunited with Kaede as they follow the boy Yumemaru who Yuki took under her care. When Samanosuke finds Yumemaru spirited off, he learns from Tokichiro that Yuki is essential for a human sacrifice where the Genmas' god Fortinbras will bless her blood that Nobunaga will drink to gain the power to destroy the Saitō clan.

After saving Yumemaru from the Genma Marcellus, Samanosuke leaves him with Kaede as he looks for Yuki underground. But as Tokichiro traps Samanosuke, Kaede is knocked out by Genma resembling Samanosuke while Yumemaru is taken by a woman. When she awakens, Kaede is led to the prison and finds Yuki locked in a cell. Guildenstern arrives and leaves Kaede to die at the hand of a powerful Genma, only for her to kill it while escaping. Samanosuke awakens and kills his doppelgänger in the underground passage. He makes his way back into the keep and finds Yumemaru with the woman who introduces herself as the Genma Hecuba as she assumes her true form while spiriting Yumemaru into the netherworld with Samanosuke in pursuit. Joined by Kaede as he learns that her kin intends to kill Yumemaru before Yuki to heighten her sorrow to make her blood more potent for Nobunaga, Samanosuke kills Hecuba. As Samanosuke makes his way through the demon door, he encounters Guildenstern who summons an improved Marcellus. After defeating him, Samanosuke makes his way into Fortinbras' throne room, where he finds Yuki and Yumemaru trapped on the upper level. Before he can free them, Fortinbras enters the room and summons Nobunaga before the monster attacks Samanosuke. After Samanosuke defeats Fortinbras, he frees Yumemaru and Yuki as Kaede enters the room.

As they flee the collapsing chamber, Samanosuke is grabbed by Fortinbras as Kaede, Yumemaru, and Yuki are forced to escape. Some of Samanosuke's blood falls on the gauntlet and activates it as it transforms him into an Onimusha. In his Onimusha state, Samanosuke kills Fortinbras by stabbing him through his central eye. As Samanosuke transforms back into a human, he encounters Nobunaga and the two have a stare off as the room continues to collapse. It is not known what happens between Samanosuke and Nobunaga. During the ending sequence, Yuki and Yumemaru follow Samanosuke's advice and travel the world while Kaede dies 14 years later in a battle (in the original ending Kaede is said to have continued to search for Samanosuke but is unable to find him, but this was corrected in Onimusha Blade Warriors that she does in fact find Samanosuke and they work together to take down the Genma). After the end credits, Samanosuke is seen alive, viewing Inabayama Castle from afar before he departs to parts unknown.