When Europeans arrived, they found a vast network of Native trails used for trade and communication, stretching from the Gulf Coast to the Great Lakes. Natives had traded items like marine shells and copper for thousands of years. Many of these trails later became major roads.

In the 1920s, William E. Myer mapped key trails, including some through West Virginia. The Great Indian Warpath was one of the most important, with branches through southwestern Virginia and the Shenandoah Valley.

Other trails in West Virginia followed river valleys, like the Kanawha, Paint Creek, Big Sandy, and Seneca trails. Today, highways like U.S. 60 and U.S. 219 follow parts of these ancient routes.