Although it is generally agreed that the area around Tarboro was settled by 1733, Mosley's map of that year shows only Tuscarora Indians. Tarrburg, as the town was called on maps of 1770-75, was chartered November 30, 1760 as Tarborough by the General Assembly. In September of the same year, Joseph and Ester Howell deeded 150 acres of their property to the Reverend James Moir, Lawrence Toole (a merchant), Captains Aquilla Sugg and Elisha Battle, and Benjamin Hart, Esquire, for five shillings and one peppercorn. As commissioners, these men were to lay out a town with lots of not more than 1/2 acre and streets not wider than 80 feet, with 12 lots and a 50-acre "common" set aside for public use. Lots were to be sold for two pounds, with the proceeds to be turned over to the Howells; however, full payment was not received for all of the 109 lots sold, and some were not sold for the 40 shillings price.

Tarboro has been the county seat of Edgecombe County since the county was established in 1741. The North Carolina State Legislature met here once in 1787 and again in 1987, and Tarboro has continued to maintain a position of importance in eastern North Carolina.

Many citizens ventured early into manufacturing, though agriculture has long been the major industry. The area prospered, and by 1850 was widely known as "Tawboro", a name attributed to "Taw", the Indian word for "river of health".

Tarboro has preserved much of its history and has developed one of the most active historic preservation programs in North Carolina. Numerous public and private residential and commercial restorations can be found in one of the largest historic districts in this part of the country. A National Historic Trail guides tourists through the older neighborhoods of the town.