The series follows Kanako Miyamae who just got transferred to an all-girls private Catholic school to find a partner of the same sex.

It started serialization in Media Factory's seinen manga magazine Monthly Comic Alive on June 27, 2006.

An anime adaptation directed by Akiyuki Shinbo and Yukihiro Miyamoto and produced by Shaft aired in Japan between January 5 and March 23, 2009 on Chiba TV, containing twelve episodes.

[8] Sentai Filmworks re-released the first season on DVD and Blu-ray with an English dub (produced at Seraphim Digital) on January 28, 2014.

[9] The opening theme is "Hanaji" by Yū Kobayashi, and the ending theme is a cover version of Yellow Magic Orchestra's 1983 single "Kimi ni, Mune Kyun" (君に、胸キュン) performed by Asami Sanada, Marina Inoue, and Yū Kobayashi, the voice actresses of the main characters.

A second anime season titled Maria†Holic: Alive, under the direction of Akiyuki Shinbo and Tomokazu Tokoro,[10] began airing on April 8, 2011.

[12] The anime opening themes for Maria†Holic: Alive are "Mōsō Senshi Miyamae Kanako" (妄想戦士 宮前かなこ) by Tomokazu Sugita (episodes 1 through 4) and "Runrunriru Ranranrara" (るんるんりる らんらんらら) by Yū Kobayashi, and the ending theme is a cover version of Linda Yamamoto's song "Dōnimo Tomaranai" (どうにもとまらない) by Ame no Kisaki Gasshōdan.