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It rises in the Appalachian Mountains in southern Upshur County, approximately 25 mi (40 km) south of Buckhannon. It follows a meandering course through the mountains generally west. It is joined by the short Buckhannon River in northeast Braxton County, near the Lewis County line. It flows northwest through the Burnsville Lake reservoir, then past Glenville and Grantsville.
In its lower reaches it follows a highly meandering course through the mountains. At Creston , it turns northwest. It receives the Hughes River approximately 12 mi (19 km) Hughes southeast of Parkersburg, where it joins the Ohio.