Catherine McAuley founded the Sisters of Mercy in 1831 in Dublin, Ireland. McAuley sought, through her service to the poor, sick and uneducated, to reveal the mercy of God in our world. With a particular concern for women, she endeavored to help them recognize their inherent dignity and become self-directing and self-sustaining. Education was at the heart of this effort, as was a desire to meet needs not addressed by others.

The first Sisters of Mercy arrived in the United States from Ireland in 1843 at the invitation of the Bishop of Pittsburgh, Pennsylvania. Their energy in ministering to the sick and economically poor attracted so many new members that by 1854, sisters had come from Ireland to settle in New York City; Chicago, Illinois; Little Rock, Arkansas; and San Francisco, California, spreading across the country and establishing schools and hospitals. 

In 1856, at the request of St. Louis Archbishop Peter J. Kenrick, six Sisters of Mercy journeyed by train and boat from New York to St. Louis, arriving on June 27, 1856, to open St. Francis Xavier Parish School. During their first year in St. Louis, in addition to opening the new school, the Sisters visited the sick, poor, and imprisoned; started a Sunday school program for African American women and girls; began an industrial school for children with one parent; and opened an orphanage. Despite challenges, including lack of money, food and clothing, the Sisters persevered with determination and faith. They expanded their ministry during the Civil War, visiting war prisoners at the hospital and jail.

Growing enrollment at St. Francis Xavier School necessitated the opening of a new school in 1871. Recognizing the ever-growing health care needs of the community, they converted the old St. Francis Xavier School to an infirmary. To meet the increased need for their health-care services, the Sisters moved the hospital to two other St. Louis sites before relocating to its current location on South New Ballas Road in St. Louis County 1963.

This focus on education continued for the Sisters of Mercy in St. Louis. More than 177 Sisters of Mercy have served in more than 20 parish elementary schools and five high schools in Missouri, including Christ the King School in University City, Mercy High School in University City, St. Joan of Arc School in South St. Louis, Annunciation School in Webster Groves, and Mercy Junior College in Webster Groves.