When Enishi was an infant, his mother died and he was raised by his older sister, Tomoe. She raised him herself, becoming both sister and mother to him, and he grew to love her quite dearly.
When Tomoe became engaged to Kiyosato Akira, Enishi reluctantly accepted him because Kiyosato truly made Tomoe happy and she loved him. Kiyosato later joined the Mimawarigumi believing that the sombre Tomoe would be happy if he became a hero, only to be killed by Hitokiri Battōsai (Himura Kenshin) for the new era. Tomoe leaves her brother behind to seek revenge, working with spies from the Shogunate to do so. Enishi becomes consumed by his loneliness to bring her back to Edo (now Tokyo) so they could be together.
When he was about ten, Enishi ran away from Edo, disappearing for seven months. He discovered the location of Tomoe through the Shogun agency and soon appeared before her, revealing that he was the Shogun agency's contact sent to Tomoe. While he believed that he was helping Tomoe's revenge, he did not know Tomoe had grown to love Kenshin, despite the fact he killed Kiyosato. She sends him away, hoping to protect Kenshin, and leaving her brother angry and confused by her actions.
After witnessing Kenshin's accidental killing of Tomoe, his hair turns snow white from the stress and grief of losing her. Enishi becomes more unstable and swears Jinchū (Man's Punishment), to be brought down on Kenshin's head for destroying his sister's happiness and then killing her. He disappears to China where he is taken in by a kind and wealthy family after suffering months of hardship in the wilderness. He later kills them all and takes their money, unable to bear seeing how happy they were.
In 1878, he returns to Japan after becoming a powerful overlord in the Chinese underworld (almost forgetting to how to speak Japanese in the process) and begins his Jinchu campaign with his "comrades".