Spice Run was named after a native shrub, Lindera benzoin — known as "spicebush" or "spicewood". The Spice Run Lumber Company created a logging boom town that harvested stands of timber to float down the Greenbrier River for the sawmills. So great were these log runs, that the waterways were choked.
In 2009, Spice Run was designated a Wilderness along with several other areas of Monongahela National Forest.