The National Park Service (NPS) was created in 1916 as an agency of the Department of the Interior and charged by Congress to manage the nation's parks. It became the primary federal agency preserving and providing for the protection, interpretation, and public enjoyment of America's most significant natural and cultural properties. The nomenclature of the NPS includes 20 titles besides national park, including such designations as national seashore and national river.

West Virginia has six National Park Service areas. The first, Harpers Ferry National Historical Park, was authorized as a national monument on June 30, 1944, commemorating Harpers Ferry's importance in the Civil War, as the site of John Brown's 1859 raid, its history as an early 19th-century industrial center, and as home to Storer College, West Virginia’s first Historically Black College and University (HBCU). It is the state’s most visited historic site. The Appalachian Trail, a National Scenic Trail, travels several miles through Monroe County and also dips into West Virginia at Harpers Ferry, where it crosses the Potomac River, as the trail winds through 14 states from Georgia to Maine. It was established in 1937 and entered the park system on October 2, 1968. The Appalachian Trail maintains a visitor center at Harpers Ferry.

Bluestone National Scenic River in the southwestern part of the state preserves 10.5 miles of the lower Bluestone River. It was authorized on October 26, 1988. Gauley River National Recreation Area, authorized the same date as the Bluestone, includes 25 miles of the Gauley River and six miles of the Meadow River. The Gauley River contains several Class V rapids, making it one of the most adventurous whitewater boating rivers in the east. The New River Gorge National River was created by the National Parks and Recreation Act of 1978 (November 10). It is a rugged whitewater river flowing northward through deep canyons. The 53-mile section from Hinton to Fayetteville is abundant in natural, scenic, historic, and recreational features. In December 2020, it was renamed New River Gorge National Park and Preserve and now encompasses more than 70,000 acres.

In 1978, the Lewis and Clark National Historic Trail was established between St. Louis and Montana to commemorate the 1803-06 Lewis and Clark Expedition. On March 12, 2019, the trail was extended 1,200 miles eastward to Pittsburgh, covering Meriwether Lewis’s first leg of the trip prior to joining William Clark in St. Louis. Known as the Eastern Legacy, this section of the trail enters West Virginia just east of Wheeling and follows Lewis’s path down the Ohio River until the river exits West Virginia at Kenova. Along the way, it passes the Ohio River Islands National Wildlife Refuge, established in 1990.

The National Park Service also partners with three National Heritage Areas in West Virginia: National Coal Heritage Area, Wheeling National Heritage Area, and Appalachian Forest National Heritage Area.

In addition, the National Park Services manages the Stephen T. Mather Training Center at Harpers Ferry, on the former site of Storer College. Interpretive park rangers from across the nation train at this center. Also at Harpers Ferry, the Harpers Ferry Center conserves curatorial artifacts and develops for parks nationwide planning documents, museum exhibits, outdoor wayside exhibits, publications, and films. West Virginia is part of the North Atlantic-Appalachian region of the National Park Service, with units in West Virginia reporting to the regional director in Philadelphia.