Founded on the Scottish model, the High School of Montreal replaced the Royal Grammar School in 1843, with the Rev. George F. Simpson as its first Rector. The direction of the High School was transferred to McGill in 1853, when it was renamed the High School of McGill College, but in 1870 the School passed under the jurisdiction of the Protestant Board of School Commissioners. The High School for Girls formed a separate division from 1875 to 1965.

The Montreal High School for Girls began in 1875 as a division of the all-male High School of Montreal. The latter had been founded in 1843 to provide a classical education (with plenty of Latin and Greek) for Protestant English-speaking boys in grades 1 to 12. McGill University controlled the boys' school (known at that time as the High School of McGill College) prior to its transfer to the Protestant Board of School Commissioners in 1870. In the years preceding the transfer, McGill University principal, J. W. Dawson, had advocated for women’s education; his idea was advanced with the opening of the girls section five years after the transfer.
One of the early graduates of the girls’ school, suffragette and physician, Olivia Ritchie, was the first female valedictorian at McGill and the first woman to earn a medical degree in Quebec. Another noteworthy student was the actress Norma Shearer.
In 1965 the boys’ and girls’ schools officially merged, although the two sexes continued to be segregated in separate wings of the neo-classical building at 3449 University Street. In 1979, the school closed its door, owing to the decline in the city’s Anglophone population; the site is now occupied by the mainly French-speaking F.A.C.E. (Fine Arts Core Education) school.