Originally called "St. Joseph's Academy for Young Ladies," the private school was founded by the Sisters of St. Joseph and was located on Power Street. 

In 1863, the Academy was incorporated in a new convent built by the Sisters of St. Joseph at the southwest corner of Bay and St. Alban's Streets, now Wellesley Street West. 

The Sisters' property, which grew to occupy a city block, housed in addition to the Academy, their Motherhouse, Novitiate and later St. Joseph's College, which was established in 1911 for women students of St. Michael's College in the University of Toronto. 

In 1928, the Academy was renamed St. Joseph's College School. 

When the Ontario government purchased the convent property to construct four office towers, the Sisters of St. Joseph relocated the College School across the street. Students helped with the move, carrying furniture across Wellesley Street. 

St. Joseph's College School at 74 Wellesley Street West opened on September 3, 1961. 

The College School became entirely publicly-funded in 1987. The Sisters leased the school to the Metropolitan Separate School Board. The last Sister of St. Joseph serving as principal retired in June 1996. 

The Toronto Catholic District School Board bought the College School property from the Sisters of St. Joseph in December 2007.