The historic Cherokee settlements were Cherokee settlements established in Southeastern North America up to the removals of the early 19th century. Several settlements had existed prior to and were initially contacted by explorers and colonists of the colonial powers as they made inroads into frontier areas. Others were established later.

In the early 18th century, an estimated 2100 Cherokee people inhabited more than sixteen towns east of the Blue Ridge Mountains and across the Piedmont plains in what was then considered Indian Country.^{[page needed]} Generally, European visitors noted only the towns with townhouses. Some of their maps included lesser settlements, but "the centers of towns were clearly marked by townhouses and plazas."

The early Cherokee towns east of the Blue Ridge Mountains were geographically divided into two regions: the Lower Towns (of the Piedmont coastal plains in what are now northeastern Georgia and western South Carolina), and the Middle/Valley/Out Towns (east of the Appalachian Mountains). A third group, the Overhill Towns, located on the western side of the Appalachian Mountains, made up the remainder of the Cherokee settlements of the time. Within each regional group, towns exhibited close economic, linguistic, and religious ties; they were often developed for miles along rivers and creeks. Satellite villages near the regional towns often bore the same or similar names to the regional centers. The minor settlements shared architecture and a common culture, but they maintained political autonomy.

No list could ever be complete of all Cherokee settlements; however, in 1755 the government of South Carolina noted several known towns and settlements. Those identified were grouped into six "hunting districts:" 1) Overhill, 2) Middle, 3) Valley, 4) Out Towns, 5) Lower Towns, and 6) the Piedmont settlements, also called Keowee towns, as they were along the Keowee River. In 1775 – May 1776, explorer and naturalist William Bartram described a total of 43 Cherokee towns in his Travels in North America, after living for a time in the area. Cherokee were living in each of them.

The Cherokee also established new settlements—or moved existing settlements—using the same or very similar names from one location to another, as the names were associated with a community of people. This practice complicated the historical recording and tracking by Europeans of many early settlement locations. Examples of this practice of repeated names include "Sugar Town," "Chota/Echota," and "Etowa/h," to name just a few.

The Lower Towns in that period were considered to be those in the northern part of the Colony of Georgia and northwestern area of the Colony of South Carolina; many were based along the Keowee River, including: the major towns of Seneca and Keowee New Towne; as well as, Cheowie, Cowee, Coweeshee, Echoee, Elejoy, Estatoie, Old Keowee, Oustanalla, Oustestee, Tomassee, Torsalla, Tosawa (also later spelled Toxaway), Torsee, and Tricentee. In addition, since the late 20th century, archeologists have identified historic Cherokee townhouses dating from the sixteenth through the early eighteenth century at the towns known as Chauga (where the Cherokee were identified as occupying it in the last of four phases) and Chattooga site, both in present-day western South Carolina; and Tugalo, in present-day northeastern Georgia. The latter site is now inundated by Lake Hartwell.

The Middle Towns of western North Carolina Colony were primarily along the upper Little Tennessee River and its tributaries. The Cherokee towns and related settlements in this area included Comastee, Cotocanahuy, Euforsee, Little Telliquo, Nayowee, Nuckasee, Steecoy, and Watoge.

Since the late 20th century, the federally recognized Eastern Band of Cherokee Indians and partners have reacquired some of these former town sites in their homeland for preservation. These include the sites of Nuckasee, Steecoy, and Watoge along the Little Tennessee River. These will be featured as part of the planned "Nikwasi-Cowee Corridor".