American Indians inhabited the area that became Wilson County for centuries before Caucasians and African-Americans moved into the Carolinas. Detailed knowledge of their history and way of life is not known, but in the 17th and 18th centuries, Tuscarora Indians lived in the area of Eastern North Carolina that would become Wilson and its surrounding counties. Of Iroquois stock, their name meant “hemp gatherers.”

The earliest European settlers in this area arrived about 1740 but they remained few in number. Most came from Virginia, rather than directly from England or the Carolina coast. At the time of the Revolution the area was still only lightly settled. British troops under General Charles Cornwallis traveled through what would become Wilson County on their trek north from Wilmington to Yorktown during the war.

Wilson County, as established in 1855, measured about thirty miles east to west and twenty miles north to south and contained 373 square miles. It straddled the vague boundary between coastal plain and piedmont. The land was almost level, with slight rolling hills especially to the west and northwest. Streams were narrow and surrounded by swampy land, particularly in the early days. The highest elevation was only 305 feet above sea level, in the northwestern corner of the county, and the lowest point fifty feet above sea level in the extreme southeast of the county. Wilson, both the center of the county and its capital, was about 138 feet above sea level. Tar and turpentine were the principal cash products at the time, with cotton becoming important in the 1860s and tobacco in the 1890s.