West Virginia Route 16 is a north–south route located in the U.S. State of West Virginia. The southern terminus of the route is at the Virginia state line in Bishop, McDowell County, where the route continues south as Virginia State Route 16. The northern terminus is at West Virginia Route 2 in St. Marys, Pleasants County, on the south bank of the Ohio River. WV 16 continues as a same-numbered route into Virginia and North Carolina, ultimately ending in Waxhaw, south of Charlotte and just north of the South Carolina border. The total length of highway is just under 475 miles long.

McDowell County is a county in the U.S. state of West Virginia. As of the 2020 census, the population was 19,111. Its county seat is Welch. McDowell County is the southernmost county in the state. It was created in 1858 by the Virginia General Assembly and named for Virginia Governor James McDowell. It became a part of West Virginia in 1863, when several Union-affiliated counties seceded from the state of Virginia during the American Civil War. McDowell County is located in the Cumberland Mountains, part of the Appalachia region.