The first white explorers to reach present-day Wise county are said to have been Thomas Walker and Christopher Gist, both in 1750.

Several forts were built all along the Clinch from 1774 onward, but only after Chickamauga Cherokee leader Bob Benge was slain in 1794 was present-day Wise considered safe for white settlers even to hunt in.

The Stonega Coke and Coal Company (SC&C) was formed in the town of Appalachia, Virginia.

[3] In July 2012 Dominion Energy built Virginia City Hybrid Energy Center in Wise County, a hybrid power plant that burns 80% coal and up to 20% biomass.

In 2014, the plant was fined $47,651 by the Virginia Department of Environmental Quality for emitting carbon monoxide and other gases at levels exceeding state regulations.

[5] The county is part of the Appalachians and has many mountainous features, including the peak of High Knob and Powell Valley.

27.40% of all households were made up of individuals, and 11.40% had someone living alone who was 65 years of age or older.

Among the unique features of Wise County are High Knob, a mountain which featured one of the last remaining Appalachian Fire Towers until its destruction by arson on October 31, 2007,[16] and the Wetlands Estonoa Project, an Appalachian Wetland and part of the Clinch River Watershed.