St. Mary's School was founded in 1900 by the Sisters of St. Francis of Penance and Christian Charity, who at the time were based in Buffalo, New York, but would soon move to Stella Niagara in nearby Lewiston, New York.

During this period, the sisters were active in the Dakotas, Nebraska, and Colorado.

[3] St. Mary's athletic teams have won a total of ten state championships.

The volleyball team has been state champions twice, in 2013 and 2014; girls' track and field twice, in 2013 and 2014.

The One Act drama performance team won the state championship in 2019.