The school was founded by Miss Margaret Scott, who served as the first Principal from 1903 to 1910. Branksome Hall was originally located in a rental property at 102 Bloor Street East, with an enrolment of 70 girls. Seven years later, that property was purchased by the province and Branksome relocated to 592 Sherbourne Street. Miss Edith Read was appointed Principal in 1910.

In 1912, the school purchased Hollydene, the elegant property at 10 Elm Avenue. Between 1912 and 1948, Principal Read added five homes to the campus and built a gymnasium and pool. She also introduced the Prefect and Clan systems and adopted the Hunting Stewart tartan for the school uniform.

Over the years, both the campus and student enrolment have expanded. Branksome’s campus now includes more than a dozen buildings, ranging from heritage mansions to modern structures, all linked by state-of-the-art technology.

In 1940, a small group of girls and staff from Sherborne Girls' School in England was evacuated to Branksome Hall. This relationship continues, with students from both schools participating in an annual exchange.