Kanako Miyamae is transferred to the all-girls Catholic school Ame no Kisaki, hoping to find true love like her parents. Because of her allergic reaction to males, she chooses this school to pursue a romantic relationship with a girl. When she meets the beautiful Mariya Shidou, Kanako thinks she has found her ideal partner. However, Mariya is actually a boy in disguise, and he blackmails Kanako into keeping his secret. Making things worse, Mariya becomes her roommate, allowing him to keep a close watch on her. The series follows Kanako's search for love amid these unexpected difficulties, especially the awkward situation of sharing a room with the mysterious and secretive Mariya.

本作では

Kanako Miyamae は真の恋愛を見つけるために女子校へ入学したが、初日に驚くほど美しい同級生のMariya Shidouと出会う。Kanakoには知られていないが、Mariya は実は男装した少年だった。この秘密を突き止めたKanakoは、彼と部屋を共有することを強要され、その生活は災難の連続となる。Mariya の執拗な干渉と、毒舌なメイドMatsurika Shinoujiの存在により、理想のガールフレンドを探すのはさらに困難になる。『Maria†Holic Alive』では、Kanakoの物語は続く。高校の混沌の中でMariyaと共に暮らし、本物の恋愛を見つけるという夢を追う。