Chizuru Yukimura heads to Kyoto to search for her father, finding herself attacked by mad men before they are cut down by members of the Shinsengumi who mistake her for a boy and take her into custody for interrogation. Upon learning that she is a girl and the daughter of a doctor who developed the Water of Life elixir that turns those that drink it into invincible blood lusting berserkers called Rasetsu (羅刹, "Furies" in English dub), the Shinsengumi decide to keep her as an aide in their search. In time, as the Shinsengumi aid the shogunate in the Bakufu, Chizuru begins to develop a bond with the Shinsengumi and its aloof member Toshizo Hijikata. However, as time passes, Chizuru and Shinsengumi confront a mysterious faction who call themselves Oni (Demons) and that Chizuru is also an Oni with father revealed to be experimenting on the Water of Life to create the Rasetsu to wipe out the human race.

《薄樱鬼》是以日本幕末时期的史实为背景改编的故事，作为奇谭的本作以独自的新要素为中心描述，因此会有和史实不一致的地方。
故事开端是幕末文久三年。 主人公‧雪村千鹤是在江户生长的兰学医（西方医学）之女。其父纲道因工作而离开江户前往京都。一开始千鹤与父亲有定期的书信往来，但很突然的，父亲不再来信，而自己写的信也得不到回应。千鹤因担心父亲而穿上男装来到京都，却没想到在那里遭遇到了冲击性的场面，并且与新选组的各位邂逅，一起寻找父亲的下落。 围绕着她的是与新选组的队士之间发生的事、自己的身世、新选组隐藏着的秘密，以及幕末的男子为了生存的战斗历程。