French Creek and the West Branch of French Creek originate in Chautauqua County in western New York and flow southwest to their confluence in Erie County, Pennsylvania, to form the main branch. The South Branch of French Creek rises in southeast Erie County near the town of Corry, PA and flows west to its confluence with the main branch near Union City. The main branch then follows a southerly route through Crawford County, the northeast corner of Mercer County, and into Venango County where it joins the Allegheny River at Franklin, PA. The main branch of French Creek is approximately 117 miles long.

The French Creek Watershed encompasses approximately 1,250 square miles of land, more than 790,000 acres. The stream and its tributaries drain parts or all of 72 municipalities in four northwestern Pennsylvania counties, and also portions of Chautauqua County, New York.

The French Creek Watershed comprises 11% of the drainage basin of the Allegheny River whose waters, in turn, flow into the Ohio and Mississippi Rivers and, ultimately, to the Gulf of Mexico. Due to its outstanding water quality, rich biodiversity, and notable history, French Creek is considered one of the most important streams of its size in the northeastern United States.