Unlike the St. Patrick High Schools that were on the city's West Side that later moved, the Sisters of Mercy were in charge of this institution on Chicago's Southeast side, beginning in 1883. It began as a parish high school of the same name, opened by pastor Martin Van De Laar, with 30 students enrolled in the one-year girls' school.

A fire destroyed the building in 1902, which led to a new combination school-church building that was ready for use on September 4 the following year. The church was on the first floor, while the school took up the second and third floors. St. Patrick offered both college preparatory and commercial courses of study, and had an affiliation with Catholic University in Washington, DC.

The school closed its doors in the spring of 1924 when St. Patrick along with four other smaller schools (St. Gabriel, St. Ita, St. James, and some students from St. Elizabeth) came together to form Mercy High School. That school would remain open until 1972 when it merged with Loretto Academy to form Unity High School, which merged with St. Thomas the Apostle in 1980 to become Unity Catholic, and later banded with Mendel and St. Willibrord to open St. Martin de Porres in 1988 (which closed in 1997).