Although the protagonist changes in every Onimusha title, he is always a skilled swordsman who embarks on a set mission which involves slaying demons and fearsome enemies during the waning years of the Sengoku period of feudal Japan. In each game, the protagonist has the ability to absorb Genma souls from defeated enemies, which help to restore health, infuse power in weapons and armor, and provide power for the elemental attacks of special weapons.

The player controls their character using the D-pad (although later games such as Onimusha 3: Demon Siege and Onimusha: Dawn of Dreams introduced analog stick control) and travels in a fairly linear method, able to rotate slowly with the input of an opposing direction. Characters tend to move slowly and can only slightly increase their speed with the dash maneuver by tapping twice in any direction. Actions common to many action-oriented games, such as jumping, grabbing, and climbing over obstacles, cannot be performed in Onimusha games.

Onimusha is very action-oriented with an emphasis on combat, and employing some horror elements. The player has an arsenal of weaponry, ranging from katana to elemental-based broadswords. The player possesses a limited supply of spiritual energy which can be used for magical attacks. These magical attacks, which vary depending upon which weapon is equipped and other offensive attributes, can be improved throughout the game by accumulation of souls from defeated enemies.

Based primarily throughout the Japanese Sengoku period, Onimusha: Warlords starts with the feudal lord Nobunaga Oda being killed during a battle. One of the prominent fighters, Hidemitsu Samanosuke Akechi, receives a letter from his cousin Princess Yuki who is concerned about servants from her castle disappearing. Samanosuke joins with the kunoichi Kaede to rescue Yuki and discover demonic creatures known as Genma. In order to defeat the Genma, the Oni clan grant Samanosuke powers from their kind. Across his fights Samanosuke discovers the Genma have resurrected Nobunaga into serving their needs while intending to sacrifice Yuki and an orphan named Yumemaru to grant him more powers. Samanosuke manages to save Yuki and Yumemaru and kills the Genma Lord, the God of Light Fortinbras. Samanosuke's group then takes different paths.

The sequel, Onimusha 2: Samurai's Destiny, has Nobunaga using the Genma in his forces to unify Japan, wiping out Yagyu village whose clan are Genma exterminators. The clan's only survivor, Jubei Yagyu, goes on a quest to avenge his clan while learning he inherited Oni powers from his mother as he uses them alongside the Oni's five orbs to battle Nobunaga's soldiers. Across his journey, Jubei meets several allies who also seek Nobunaga's life. Jubei manages to infiltrate Gifu castle and confronts Nobunaga alone. Although Jubei kills Nobunaga, the warlord's soul escapes and later reconstitutes himself. The spin-off Onimusha: Blade Warriors has the cast from Warlords and Samurai's Destiny in a new battle against Nobunaga's forces.

The third game, Onimusha 3: Demon Siege, has Samanosuke's clan attacking the Oda forces again. Before confronting Nobunaga, Samanosuke is transported to Modern Paris as a result of an experiment made by the Genma scientist Guildernstern to enable his kin to conquer more lands. In the meantime, service agent Jacques Blanc is a victim of Guildernstern while transported to Japan's Sengoku period. There, Jacques is granted Oni powers by an Oni who tells him to join forces with this timeline's Samanosuke and defeat Nobunaga if he wishes to return home. While Jacques aids Samanosuke in the past, in the future Samanosuke is helped by Jacques' family to investigate the Genma. In the end, the two Oni warriors are successful in stopping the invasion and returning to their respective times. Samanosuke manages to slay Nobunaga and seal his soul within the Oni Gauntlet to avoid another resurrection.

The fourth game, Onimusha: Dawn of Dreams, had Nobunaga's servant Hideyoshi Toyotomi unified Japan with the Genma whom he supported in their actions. His illegitimate son, Hideyasu "Soki" Yuki, goes on a quest to defeat Hideyoshi and stop the Genma. He is aided by several other warriors, including an elder Samanosuke who recognizes him as the Black Oni, the God of Darkness. After mastering his Oni powers, Soki joins with his friends to defeat Hideyoshi's army. In the aftermath, it is revealed that Hideyoshi was a mere puppet of the Genma Triumvirate who wish to resurrect Fortinbras at his full power as the Genmas' God of Light. Although the Genma Triumvirate and Hideyoshi are defeated, Fortinbras resurrects with Soki using the Oni Gauntlet to destroy the Genma and restore the country's peace at the cost of his life. Soon after, Samanosuke embarks on a quest to seal away the Oni Gauntlet t…

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Samanosuke Akechi (明智 左馬之介 秀満 Akechi Samanosuke Hidemitsu), later also known under the moniker Tenkai Nankōbō during his appearance in Onimusha: Dawn of Dreams, is the main protagonist of the first and third installments in the Onimusha series: Onimusha: Warlords for the PlayStation 2, Xbox and Windows, and Onimusha 3: Demon Siege for the PlayStation 2 and Windows. He also appears as a supporting playable character in the fourth game Onimusha: Dawn of Dreams, and as one of the combatants in Onimusha: Blade Warriors, both on the PlayStation 2. He is loosely based on the historical figure, Akechi Hidemitsu. His in-game model is based and voiced by Takeshi Kaneshiro. Samanosuke is the only character to appear in all four mainline Onimusha games. He appears in Onimusha 2 in a flashback drawing.

Jūbei Yagyū is the main protagonist of Onimusha 2: Samurai's Destiny. As the first leader of the Yagyū clan seen in the series and originator of Shin-in style sword combat, he was born as Sougen but later given the name Jūbei as a child, a tradition which would continue as seen with his granddaughter. His father was the late Head of the Yagyū clan, who was seduced and had a child by a woman who disappeared shortly thereafter. Jūbei never knew his mother, but does meet his mother during the events of Samurai's Destiny. His in-game character is modeled after late Japanese actor Matsuda Yusaku.

Hideyasu "Sōki" Yūki is the main protagonist in Onimusha: Dawn of Dreams. He is the biological son of Ieyasu Tokugawa and a warrior who possesses the dark power of the Oni. He goes by many names besides Sōki and Hideyasu Yuki: Blue Demon and Oni of the Ash. Having Lamentation, his prized broadsword he learned about Hideyoshi's insidious scheme, he sets out on a journey to burn the Genma trees and defeat the Genma running rampant across the land. He is the first Onimusha main character to not be modeled after an actor. He is also the only main character to be killed, dying at the end of Dawn of Dreams after sacrificing himself to destroy the Oni Star. Soki has appeared as a playable character in Tatsunoko vs. Capcom: Ultimate All-Stars.

Jacques Blanc is one of two main protagonists (the other being Samanosuke Akechi) in Onimusha 3: Demon Siege. Working as a policeman, he is the first Westerner who wields the Oni Power, originating from France. He is modeled after French actor Jean Reno.

Nobunaga Oda (織田信長) is the main antagonist in the first three Onimusha games, in particular Onimusha 2: Samurai's Destiny and Onimusha 3: Demon Siege, where he is the final boss in those two games. In real world history, Nobunaga is viewed culturally as both a hero and as a villain for respectively trying to unite his nation during the Sengoku Period and the horrific lengths he took to achieve his goal. In this timeline he forms an alliance with the demons for power and to conquer Japan. Despite being killed at the beginning of Onimusha: Warlords, he returns as a demon. He battles Jubei at the end of Samurai's Destiny but due to Jubei not having an Oni Gauntlet to seal his soul, his death was only temporary. He returns in Demon Siege after being revived by the demons again. He is finally killed by Samanosuke and sealed in his Oni Gauntlet.

Fortinbras …

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