The river flows from the Orangeville Reservoir in the town of Orangeville, Dufferin County, through the Niagara Escarpment[2] and the Minesing Wetlands, the latter a wetland of international significance (Ramsar Convention site), and empties into Nottawasaga Bay, an inlet of Georgian Bay on Lake Huron, at the town of Wasaga Beach, Simcoe County.

The Nottawasaga River is the resting home of HMS Nancy, a merchant schooner taken into the Royal Navy during the War of 1812.

They rowed 360 miles to Fort Michilimackinac and three days later, Worsley returned with 92 men to take the Tigress and Scorpion.

The hull is now preserved in a museum at Nancy Island Historic Site which is a part of Wasaga Beach Provincial Park.

Fish ladders allow rainbow trout to reach spawning grounds on the upper river.