In September 1931, South Side Catholic High School opened with Christian Brothers teaching in two classrooms, small buildings on the premises of St. Joseph's Orphanage.

[2] When a new, $1.5 million building was completed in 1964, there were 883 students in 19 classrooms, besides three laboratories for science and one for languages, a library, cafeteria, administrative offices, and rooms for 30 Marianists on the third floor.

[2] The original gymnasium of 1938 was destroyed by fire in 1993 and replaced with a new complex named for Archbishop John L. May.

In 2000, renovations included converting the Marianist quarters into a fine arts center and band room.

The Archdiocese of St. Louis and the United States Province of the Society of Mary continue to sponsor the school, and 19 faculty members have become lay Marianists.