The Virginia General Assembly created Pendleton County in 1788 from parts of Augusta, Hardy, and Rockingham counties. The name honored Edmund Pendleton, who lived from 1721 to 1803 - a Virginia statesman and jurist, member of the Continental Congress, and first president of the Virginia Supreme Court of Appeals. By the 1740s, three valleys of the area had been named by white hunters and prospectors. German families pushed up the South Branch Potomac valley from Pennsylvania and the Shenandoah. Scotch-Irish families came northwest from Staunton, Virginia toward the headwaters of the James River. The two streams of immigration converged in Pendleton, producing a county with both German and Scotch-Irish traditions, both Lutheran and Presbyterian churches, and a mix of cultural patterns that distinguished it from neighboring counties.

Pendleton was divided in the Civil War. The northern section, including the Smoke Hole community, was staunchly Unionist. The communities of the upper North Fork - Germany Valley, Franklin - were strongly Confederate. In June 1863, the federal government included Pendleton County in the newly formed state of West Virginia against the wishes of many of the inhabitants. That fall, Union General W.W. Averell swept up the South Branch valley and destroyed the Confederate saltpeter works above Franklin - the same Schoolhouse Cave operation that had supported Hinkle's Fort during the French and Indian War nearly a century earlier. The county survived the war as a border zone, divided enough that the conflicts among neighbors continued long after Appomattox.

Spruce Knob - the highest point in West Virginia and in the entire Allegheny range at 4,863 feet - sits in Pendleton County. Significant portions of the Monongahela and George Washington National Forests cover the county, along with parts of the Spruce Knob-Seneca Rocks National Recreation Area. The Germany Valley Karst Area and the Sinnett-Thorn Mountain Cave System are designated National Natural Landmarks. The western part of the county also falls within the National Radio Quiet Zone, so cell service is patchy. The protected lands and the federal restrictions have kept Pendleton from developing the way other counties have - the absence of cell towers, big-box stores, and four-lane highways is, in a real sense, federal policy.

The economy mostly runs on small to medium-sized farms and small businesses. Franklin, the county's only incorporated town, holds most of the commerce. The North Fork Valley on the west side caters to outdoor recreation visitors with motels, restaurants, and guide services. In recent years, maple syrup has become a notable growth industry - Dry Fork Maple Works, the state's largest maple sugaring operation, is based in Pendleton, though its actual sugaring happens mostly in neighboring Randolph County. Several non-profits with national reach are headquartered here, including Almost Heaven Habitat for Humanity, Future Generations, The Mountain Institute, and Mountain Springs Farm and Heritage Center. The NSA's Sugar Grove Station - an electronic listening post for the National Security Agency - sits near the southeast corner of the county.

On Election Day in November 1985, the remnants of Hurricane Juan combined with a cold front and dumped extraordinary rainfall on the central Appalachians. The South Branch of the Potomac at Franklin crested at 22.6 feet - more than 15 feet above flood stage in the shallow riverbed. Bridges washed out. Houses were swept away. Sixty-two people were killed across West Virginia, Virginia, Maryland, and Pennsylvania. Thirty-eight of those deaths occurred in Pendleton and Grant counties, according to the National Weather Service. Locally, the storm became known as the 'Killer Floods of 1985.' Virginia called them the '1985 Election Day Floods.' The riverside communities that were destroyed have been rebuilt or relocated. The flood marks on Franklin's older buildings remain. The narrow valleys that drew Abraham Burner here in 1745, with their fifty wading deer, are the same valleys that channel floodwater with no place to go.