The land on which the St. Lawrence neighbourhood is built was originally part of the shoreline of Lake Ontario. Immediately to the north, above Front Street, was the Town of York, the forerunner to the City of Toronto.

The site of the present day St. Lawrence neighbourhood was created from landfill in the early 1800's. It was originally intended to serve as a public promenade with a grand Esplanade along the waterfront, however the city turned the land over to the railways, which in turn attracted industry to the St. Lawrence area.

By the early 1900's, St. Lawrence had become one of Toronto's most prominent industrial centres. It remained a vital industrial area until the late 1940's, when Toronto's industrial base began moving outside of the city.

Consequently, St. Lawrence went into a period of decline which lasted until the 1970's, when Toronto politicians made the decision to create the present day vibrant St. Lawrence neighbourhood.