The town of York was established in 1793, on a site of ten blocks north of Front Street between George and Berkeley Streets. The area of today's St. Lawrence neighborhood was then below the waterline, the shoreline being just south of Front Street. St. Lawrence was the first industrial area of York.

By the early 1900's, St. Lawrence had become one of Toronto's most distinguished industrial centers. It persist a crucial industrial area until the late 1940's, when Toronto's industrial base began moving outside of the city.

The first Toronto’s government, industry and commercial centers were situated in St. Lawrence.

Diverse important historical buildings are still standing on the fringe of the neighborhood including: the South St. Lawrence Market which served as Toronto's first City Hall, the North St. Lawrence Market which was Toronto's first official farmers market, the iconic Gooderham Flat Iron building which was the offices for the Gooderham financial empire, the King Edward Hotel designed by E.J. Lennox the architect of Casa Loma, St. James Cathedral which has the tallest spire in Canada, and St. Lawrence Hall which was the cultural and social center of early Toronto.