St. Mary School was established in 1891 by the Benedictine Sisters. On August 27, 1902, four sisters from the School Sisters of Notre Dame filled with enthusiasm and faith arrived in Gainesville to take charge of the school which was then a six-room frame building. On September 8, 1902, St. Mary Day School was openend. Thirty-two pupils were enrolled that August which increased to seventy-five by the end of the year. The next school term 120 students enrolled.
In 1905 high school subjects were offered for the first time and on June 11, 1906, St. Mary School had its first graduating seniors.