Jacob Marlin and Stephen Sewell are often considered the first European settlers in the area, arriving near present-day Marlinton around 1749 and staying until at least 1751. Permanent settlement began in the early 1750s, but many settlers left due to Indian attacks during the French and Indian War. People began settling again in 1761, but attacks continued through the Revolutionary War and into the early 1790s.

By the time of the Civil War, road improvements had made travel easier, reducing isolation. Turnpikes between Warm Springs, Lewisburg, Huttonsville, and Parkersburg helped, and in 1854-56, a bridge was built at Marlins Bottom (now Marlinton).

Schools date back to the 1790s, with a big improvement in 1842, when three academies began preparing students to attend the University of Virginia. The first church was the White Pole Meeting House, built before the Revolutionary War, and still exists as Wesley Chapel United Methodist Church in Hillsboro. Presbyterian services started in Hillsboro between 1783-1788.

The fertile lands in Little Levels helped start the livestock industry, which is still important. Slavery was present early on, but not in large numbers due to the small sizes of the farms.