[2] The area of far western Virginia and eastern Kentucky supported large Archaic Native American populations.

Lee County was the final front on the Kentucky Trace, now known as the Wilderness Road and The Trail of the Lonesome Pine.

During the 1780s and 1790s, fortified buildings called "stations" were built along the trail for shelter from Indian raids as the settlers followed Daniel Boone's path into the Kentucky frontier.

The economy of Lee County has been based largely on growing tobacco and mining coal.

Lee County shares Cumberland Gap National Historical Park with Kentucky and Tennessee.

[5] Lee County is one of the 423 counties served by the Appalachian Regional Commission,[6] and it is identified as part of "Greater Appalachia" by Colin Woodard in his book American Nations: A History of the Eleven Rival Regional Cultures of North America.

The entirety of Lee County is physically closer to eight state capitals other than its own capital in Richmond: Raleigh, North Carolina; Columbia, South Carolina; Atlanta, Georgia; Nashville, Tennessee; Charleston, West Virginia; Frankfort, Kentucky; Columbus, Ohio; and Indianapolis, Indiana.

Additionally, the far western part of Lee County–including Wheeler and the Cumberland Gap, roughly 350 miles (560 km) from Richmond–is closer to Montgomery, Alabama, a ninth state capital.

[20] Voters in Lee County wavered between Democratic and Republican presidential candidates throughout much of the twentieth century.

Since the beginning of the twenty-first century, the county has become more consistently Republican, giving Donald Trump over 80% of the vote in all three of his campaigns.

Pennington Elementary School, consisting of three buildings built at various times (1912, 1917, and 1937), was demolished in 1989, and a bank was constructed on its Morgan Avenue site.