Secluded in the Allegheny Highlands, present-day Monroe County remained a land unseen for several generations of early Virginia colonists. The first settlers arrived around 1760, beginning a 30-year period of frontier conflict. Formation of Monroe as a separated County, separated from Greenbrier, came in 1799. The new County was named for James Monroe, Virginia's governor at the time.

Monroe's economic basis has always been farming and timber harvesting. Beginning around 1790, two additional activities were important for about 70 years. It was the age of water power, and streams such as Indian Creek and The Second Creek supported more than two dozen water-powered mills. During the same period, the area's mineral springs became major summer resorts, catering to Southerners seeking relief from lowland summer heat.

Monroe County supported the Confederate cause during the War between the States. When the Federal side carved the new State of West Virginia from Virginia in 1863 included Monroe County, a designation resisted by residents until 1865.

After the War, with the South's economy and social order devastated, the old resorts faded away. New railroads came nearby, but bypassed Monroe County except at more accessible edges. Steam power and newer forms of energy overshadowed water power. Lacking suitable coal deposits, Monroe County lies outside the area which encompasses most of West Virginia. For these reasons, "Old Monroe" relies largely on agriculture and retains its pastoral character. In recent times tranquil landscapes has attracted a number of artisans, retirees, and knowledge worker