Henry County played a role in the development of the Colonial Frontier with the Carolina Road Beginning around the 1740s, this was the primary corridor funneling settlers from Pennsylvania to the settlements in the Carolina backcountry - particularly the Moravian Wachovia Tract. It is estimated that by the 1760s, some 1,000 wagons a day were traveling the Carolina Road. The Carolina Road followed the path of the Smith River that runs through Henry County to North Carolina.

Initial settlement of present-day Henry County coincides with the road. Settlers represented diverse cultural backgrounds: Germans, Welsh, Scots-Irish, English and African. Local historian Sally K. Burns has taken a 1753 Moravian diary describing passage through Henry County and traced the route in relation to today's landscape.