Hertford County is home of the Meherrin Indian Tribe, descendants of indigenous people who had inhabited the region for many centuries.

After decades of encroachment by English colonists, the Tribe moved south from Virginia, where they settled in 1706 on a reservation abandoned by the Chowanoke.

[citation needed] European explorers and surveyors visited the land in the late 1500s and 1600s.

[5] Early settlers were of English, Scottish, Scotch-Irish, Irish, and French descent.

[7] A new county was first proposed by Representative John Campbell of the North Carolina colonial legislature on December 12, 1758, when he presented the body with a petition from area residents who were frustrated by the distances they had to travel to attend court sessions.

[10] The county court convened at Cotton's Ferry until the town of Winton was incorporated upon land gifted by Wynns and designated the seat of government in 1766,[11][12] and a courthouse was subsequently constructed.

[14] Hertford's economy prospered in the Antebellum period, underpinned by slavery-supported agriculture and the use of the Meherrin and Chowan rivers as trade routes to southern Virginia.

[16] Men from Hertford County served in several Confederate States Army infantry and cavalry units.

[17] Federal forces intervened in eastern North Carolina early in the conflict, and in February 1862 they captured Roanoke Island,[16] exposing territory along the Chowan River vulnerable to further penetration.

[17] Federal gunboats were subsequently dispatched up the river to destroy rail bridges north of Winton but were repulsed in an ambush by Confederate artillery.

[22] The railroad fueled growth in Ahoskie, drawing industry and leading it to surpass Winton as the county's most economically significant town.

[9] Damage to cotton crops by the boll weevil in the early 1900s led the county's agricultural sector to diversify into livestock as well as tobacco and the production of fruits and vegetables.

[33] Rivers Correctional Institution, a private prison operated by the GEO Group which operates under contract from the Federal Bureau of Prisons and houses many felons who committed crimes in Washington, DC, is 1 mile (1.6 km) from Winton.

The larger area has historically lagged behind the rest of the state in terms of economic development.