[9] The Archdiocese of Los Angeles opened Mater Dei in 1950, the first Catholic high school in Orange County.

Overcrowding persisted until 1987, when Santa Margarita Catholic High School opened in South Orange County.

[13][14][15] In 2021, a lawsuit was filed alleging that systemic hazing pervaded the football program resulting in a "brutal locker room altercation.

[18] Orange County bishop Kevin Vann responded with a public statement supporting the school's leadership and criticizing the "media frenzy".

[20] In January 2022, a female alumna of Mater Dei filed a lawsuit following the surfacing accusations of hazing, alleging that she was sexually assaulted by a former football coach during the late 1980s.

[22] Known for their football and basketball programs, Mater Dei has also graduated professional athletes Robbie Rogers (soccer), Tiki Ghosn (mixed martial arts), and Greg Woepse (pole vault), as well as ten Olympians.