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St. Mary's School was built in 1913 and opened in February, 1914, the first school built by the new Separate School Board in Saskatoon.  The board was elected in 1912 after petitioning the provincial government in 1911 for its establishment.  Classes for a separate school were begun in the basement of St. Pauls' Catholic Church on Spadina Crescent but it was felt that this was insufficient and there was a need for a school catering to the needs of Roman Catholic children on the west side of the city.  So the fledgling board began was to be a long process to establish St. Mary School.

Architect David Webster began drawing up plans for the school in 1912.  Webster was a well-respected architect in the city with many buildings to his credit, including the historic Legion Building in downtown Saskatoon.  He designed the castle schools including Caswell School and St. Mary School. In May 1913 the Daily Star reported the contract for the construction of the building at a cost of $83,500 was awarded to Messrs Shannon Bros and Cassidy.  The design of brick and stone was to have eight classrooms, fully modern in style and architecture.  On July, 1913, the cornerstone for the new school was laid by Rev. Father Lacoste with remarks made by attending board members, a local businessperson, R. J. Barry, owner of the Barry Hotel.  The newspaper report also stated copies of the daily papers, a history of the school with some coins of the 'present day' were buried under the stone.  The school opened on February 16, 1914 with six teachers and about 160 students.

By the fall of 1914, T.H. Creighton was principal.  In 1915, J.E. McDonald and a staff of lay teachers took over.  Three other teaching orders joined the staff over the next decades.  In 1927, E.D. Feehan took over as principal and fulfilled that role until 1951, giving consistency for the school and the students.

St. Mary School had three floors and a basement and from the beginning, the plans were to make as much use of the space as possible.  The first floor had four classrooms and the principal's room.  The second floor had four more classrooms and two teachers' rooms.  The third floor was set aside for the accommodation of the janitor and aa assembly room.  The basement held the boys' lavatory and playroom and the girls' lavatory and playroom as well as a manual training room and the boiler room.

St. Mary's Parish held services in the basement until the first St. Mary's Church was built on 21st Street.  From 1922 till 1932, the Sisters of Loretto joined the staff and had accommodation on the third floor. 

By the end of World War Ii, the school had grown to need ten classrooms – two in the basement.  The city had grown around the school.  The school was renovated and changed over the years but retained much of its original exterior.  The historic St. Mary School building provided a variety of facilities in the community, fulfilling a heritage role in Pleasant Hill.

The building was replaced by the new St. Mary's Wellness & Education Centre, which opened in 2012.  The new building includes a medical clinic for students and the community.  It also has a daycare, optometry clinic, and an expanded pediatric clinic for kids – the first of its kind in Canada.  The school includes a fully equipped gym and walking track, and a specially ventilated room for cultural activities.  ​