Originating near the Wells Gray Provincial Park, it flows into Quesnel Lake, the source of the Quesnel River which in turn is a major tributary of the Fraser River.

The Horsefly River is the largest inflow for Quesnel Lake, draining 2750 km2 of the Interior Plateau.

It is also a spawning ground for sockeye, chinook and coho salmon.

Fossil insects, fish and plants have been collected from Eocene Epoch lake sediments exposed along the river banks.

This article related to a river in the Interior of British Columbia, Canada is a stub.