The Brothers of the Christian Schools arrived in Montreal in 1837 and founded the first permanent community of De La Salle Brothers in North America . At the request of Bishop De Charbonnel, five Brothers came to Toronto in 1851 and there established a grammar school at the corner of Lombard and Jarvis Streets. Twenty years later, the school was extended to include secondary education and was relocated to what was then the Bank of Upper Canada. The name De La Salle Institute was changed to De La Salle College in 1880 when university entrance courses were added to the commercial curriculum. This building still stands at the corner of Adelaide and George Streets.
The next major step occurred in 1913 when De La Salle College took over part of the 67 Bond Street building, right next to St. Michael's Cathedral. In 1925, the senior section was relocated in what is now Our Lady of Perpetual Help School. In 1932 and 1933, these classes were moved to De La Salle College "Oaklands" which had opened in 1931.

"Oaklands" was once part of the Crown Lands deeded to Honourable John Elmsley in 1798. In 1858, Senator John Macdonald acquired 45 hectares of it and built what is at present the residence of the Brothers. The Brothers of the Christian Schools bought 20 acres of the property in 1931 and turned it into a boys' school. Brother Alfred was the guiding genius in acquiring the property and became the school's first Director/Principal.
In 1950, after a great deal of effort and sacrifice on the part of the Brothers and the alumni of the school, the present structure was officially opened. De La Salle had always been a completely private school, but in 1967 a very significant change took place when grades nine and ten were placed under the auspices of the Metropolitan Separate School Board (MSSB). By 1987, the entire high school was under the MSSB, now the Toronto District Catholic School Board.
After much ongoing thought and discussion, the Brothers of the Christian Schools determined that returning the school to its former independent status would best meet the spiritual and educational needs of the Catholic community they are called to serve. In September 1994, De La Salle College "Oaklands" again reopened its doors as an independent, now co-educational, university preparatory school.