The Sisters of the Blessed Sacrament founded, owned and operated the school, having opened it in 1915 as what would eventually become Xavier University of Louisiana.

[2] Andrew Vanacore of The Times Picayune wrote in 2013 that "Xavier Prep has evolved over nearly a century into a symbol of achievement for girls from the city's black middle class.

Xavier Prep was established in 1915 by Saint Katharine Drexel; its first president was a Josephite priest.

[2] It was originally intended to be a revival of Southern University, which had recently relocated from Uptown New Orleans to Baton Rouge due to racist opposition to an HBCU being in the neighborhood.

The university would relocate to its current location in Gert Town while the high school remained uptown.