Indigenous folks had used and maintained much of the path for their expansive trading network for centuries prior to its use by Europeans and/or European-Americans.
In early colonial times, Virginian traders used the path to travel to Native American towns in the Waxhaws.
They led long pack caravans of horses carrying "loads of guns, gunpowder, knives, jewelry, blankets, and hatchets, among other goods", and travel southwest to Indigenous villages along the journey to the Waxhaws region, in the vicinity of present-day Mecklenburg County.
Because the path was well laid out through the complex geography of the piedmont area, connecting fords of many streams, it was roughly followed by the 19th-century railroad.
The Piedmont Urban Crescent essentially has developed along the Trading Path, and since the late 19th century has had steady growth.