The Guyandotte River is a tributary of the Ohio River, approximately 166 mi (267 km) long, in southwestern West Virginia in the United States. It was named after the French term for the Wendat Native Americans. It drains an area of the unglaciated Allegheny Plateau south of the Ohio between the watersheds of the Kanawha River to the northeast and Twelvepole Creek and the Big Sandy River to the southwest. Via the Ohio River, it is part of the Mississippi River watershed.

Wyoming County is a county in the U.S. state of West Virginia. As of the 2020 census, the population was 21,382. Its county seat is Pineville. The county was created in 1850 from Logan County and named for the Lenape word meaning "large plains".