Like most early counties on the eastern side of the early North Carolina colony, Granville was site of the Tuscarora uprising. Once the natives were defeated in the Tuscarora War, Virginia farmers and their families settled Granville County, where they concentrated on tobacco as a commodity crop. The economy of the region was dependent on slave labor, as tobacco was very labor-intensive to cultivate and process. By the start of the Civil War, Granville planters worked more than 10,000 slaves on their farms, at a time when total county population was 23,396.