The creek's lower reaches flow through urban areas of Thorold and St. Catharines and has been heavily altered by human activity for almost two centuries.

The creek was first known as "Ashquasing" by the Mississaugas Indigenous people, the name meaning "that which lies at the end" in the Anishinaabe language.

This may be grouped into six sub-watersheds:[3] Of these, only the Upper Twelve Mile Creek can truly be considered to retain any significant degree of its natural state.

The area containing the headwaters is known as the Fonthill Kame Delta Complex and was formed from debris left behind by glaciers as they retreated approximately 12,000 years ago.

Township maps from the latter half of the 19th century show a meandering stream flowing through this area (Beaverdams Creek) and plunging over the Niagara Escarpment at Decew Falls.

It emerges from the tunnel and joins with the main branch of the Twelve Mile Creek immediately beside Highway 406, and not far from the downtown buildings of St.

[3] The lower portion of Twelve Mile Creek, while historically navigable as part of the second Welland Canal, is now a fast flowing river with rapids and a wide, swift water course.

The water flows over a weir into Port Dalhousie harbour, and finally out into Lake Ontario between two long piers.

In the period following the War of 1812, assorted mills made use of water power from various creeks which flowed over Niagara Escarpment.

Merritt's mills were plagued by low water conditions, especially in late summer - exactly when the grain harvest needed to be ground.

[8] Twelve Mile Creek was not necessarily the best route for the canal, but it was the location of Merritt's mills, so economic motivation became a factor.

The lower reaches are not in anything resembling a natural state, having been straightened, dredged and fed massively increased water flows.