Over the years the Road led countless Scotch-Irish, Germanic, and English settlers southward from Philadelphia to settle the Appalachian uplands from Pennsylvania to Georgia. Over the Road went the progenitors of John Sevier of Tennessee, John Caldwell Calhoun of South Carolina, Sam Houston of Texas, Cyrus McCormick of Virginia, and other Americans.
Countless cities and towns from Philadelphia to Augusta, Georgia, owe their beginning to early camp sites along the Road that grew into tavern locations, then into county seats, and then into centers of agriculture and industry. Today such Wagon Road towns as Lancaster, York, and Gettysburg, Pennsylvania; Harper's Ferry, West Virginia; Winchester, Newmarket, Harrisonburg, Staunton, Lexington, and Rocky Mount, Virginia; Winston-Salem, Salisbury, and Charlotte, North Carolina; and Newberry and Camden, South Carolina have grown along the onetime settler's trail.
The Great Wagon Road also tells of Daniel Boone's pioneering from Big Lick, Virginia-now Roanoke-into the territory of Kentucky. Boone Expedited western settlement by cutting a trail across Cumberland Gap on Virginia's frontier to lead settlers in Revolutionary years into dangerous Indian country.