Originally located in the Italian Hill district of St. Louis, its first principal was Sr. Anita Marie Giampetro.

[5] During a June 9–17, 2012, tour in Rome, the Cor Jesu Academy choir performed for Pope Benedict XVI during the June 13 papal audience[6] and was the principal choir for a Mass at the Altar of the Chair in St. Peter's Basilica, singing the liturgy for the feast of the Sacred Heart at Santa Croce.

It also presented a formal concert at St. Ignatius Church in Rome and sang at a liturgy at the Basilica of St. Francis in Assisi.

Louis along with Advanced Placement courses in History, Government, English, Spanish, French, Latin, Math, and Science.

According to St Louis Magazine, the average score of 29 was the highest for an all-girls Catholic High School.