The Saponi Indians originally lived in the Virginia Piedmont. English pioneer John Smith encountered the tribe in 1607. Later on, German explorer John Lederer encountered the tribe in 1670 living on the banks of the Staunton River. At the time the Saponi and Tutelo were living close together in a village southwest of present-day Lynchburg. Thirty-one years later John Lederer found the tribe living along the Yadkin River to evade attacks by enemies. Shortly after, the Saponi and Tutelo migrated to a new area called Sapona Town, close to present-day Windsor, North Carolina.
In 1714, the Saponi, Occaneechi and Tutelo signed a treaty with Virginia governor Alexander Spotswood. The tribes later settled in Brunswick County, Virginia on a small reservation named Fort Christanna along the Meherrin River. By 1729 Fort Christanna was deserted due to tribal warfare with the Iroquois. The Saponi migrated south towards the Catawba River to settle with the Catawba Nation.
By 1731 the desire to live autonomously led to Saponi secession from the Catawba Nation. Many Saponi migrated to New York with the Cayuga tribe and some inhabited colonial areas. Many also stayed in North Carolina to fight against the colonists in the Tuscarora War. By 1740, many Saponi and Tutelo migrated north to Shamokin, Pennsylvania and in 1753 the Cayuga tribe selected the Saponi and Tutelo to join them in the Six Nations. After this point, records are scarce concerning the Saponi.