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In the Sengoku period of Japan, a young orphan named Kotarou and his dog Tobimaru steal from unsuspecting villagers in order to make ends meet. However, Kotarou is forced to remain on the run when he finds himself being hunted down by assassins sent by China's Ming Dynasty for mysterious reasons not involving his petty crimes. Fortunately, the duo run into Nanashi, a ronin who has taken refuge in a small temple, when Kotarou is attacked and Tobimaru poisoned. Although the samurai saves the helpless pair from their pursuers, he feels that there is no need to help them further; but when offered a gem in exchange for his services as a bodyguard, he reluctantly accepts Kotarou's offer of employment—just until Tobimaru is healed and the two reach their destination. As the three set out on a perilous journey, it soon becomes evident that their path is riddled with danger, as the Ming Dynasty has now sent a terrifying swordsman after them to capture Kotarou and fulfill a certain prophecy.[Written by MAL Rewrite]

After Jinta and Suzune ran away from their home as children, they were taken in by Motoharu—the virtuous sentinel of Kadono Village—and his daughter, Shirayuki. The settlement was ruled by its shrine maiden, Itsukihime, whom only a select few were allowed to interact with. When Itsukihime passed away, Shirayuki was appointed in her place. Wishing to stay in contact with her, Jinta worked diligently for years and was finally selected as the next sentinel. As the protector of the village, Jinta's duty is to eliminate any threats. One day, he encounters a demon in a nearby forest. At the end of the battle, the demon makes a proclamation about the destined ruler of all demonkind. He attaches his severed arm to Jinta, turning him into an unaging demon man. By the time Jinta comes to, Kadono is on fire. Suzune has transformed into the demon from the divination, and due to a series of misunderstandings, she murders Shirayuki and flees. Devastated, Jinta cannot forgive Suzune for her actions; he departs on a journey to find her. As Jinta travels around Japan across the eras, he endeavors to protect as many people as possible from aggressive demons. In his quiet moments, he contemplates what he should do when he once again faces his childhood friend.