Father William Anthony Hughes, later the Bishop of Covington, Kentucky, was named the school's first principal.

The initial faculty included sisters from the Ursuline, Dominican, Notre Dame and Vincentian communities, two priests and five lay teachers.

In early 2000, Cardinal Mooney came into possession of the two military annex buildings adjacent to the school grounds.

Shortly after obtaining this real estate, construction of the high school's new sports complex was underway.

The U.S. Army and U.S. Navy annex buildings were left standing during construction, but Rush Boulevard was filled in with top soil and cut off from the rear lot.

However, his approval was met with stipulations that included proof of sufficient financial support for both a new high school building as well as an endowment fund to provide scholarships for students who face poverty and other social constraints.