Before the arrival of European colonists, the Tuscarora people's homeland included much of North Carolina's coastal plain. The historic nation was composed of separate factions, and by 1710 the most notable of these were the Upper Town Tuscarora (near present-day Bertie County) and the Lower Town Tuscarora (near present-day Craven County). While the Upper Town Tuscarora were led by Chief Tom Blount, the Lower Town Tuscarora, sometimes called the Kahtehnuʔá·ka·ʔ, or "People of the Submerged Pine tree," were led by Chief Hancock. Over time, the behavior of the colonists—their expansion outside the Albemarle Region, their enslavement of Indian people, and their ruthless trading practices—alarmed the Tuscarora, most especially the Lower Town Tuscarora, and tensions between them and the colonists escalated.

These escalating tensions resulted in an armed conflict known as the Tuscarora War. The war devastated the Lower Town Tuscarora, their losses estimated to be 1,000 Tuscarora people captured or enslaved and 1,400 killed. Over the next several decades, many who survived the conflict traveled north to New York to join the Haudenosaunee, or Iroquois League. Those who remained with the Upper Town Tuscarora relocated to a reservation along the Roanoke River in southwestern Bertie County and remained under Chief Tom Blount's leadership.

In 1754, Arthur Dobbs reported that 100 Tuscarora men and 200 women and children visited New Bern to make their acknowledgements to Dobbs as the new colonial governor and petition for better enforcement of their hunting rights. Later in 1758, a small group of Tuscarora warriors in North Carolina allied with the British during the French and Indian War. In 1763 Dobbs reported that the Tuscarora nation's population in North Carolina had been reduced to below 100 warriors.

Today, enrolled members of the federally recognized Tuscarora Nation reside in New York, but Tuscarora-identifying people have organized into several smaller communities in and around Robeson County, North Carolina: the Tuscarora Nation East of the Mountain, the Tuscarora Tribe of North Carolina, the Tuscarora Nation of Indians, the Southern Band Tuscarora Indian Tribe, and the Tuscarora Nation of North Carolina. As of 2023, none of these have been recognized by state or federal governments.

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