The first federal Indian reservation was established in 1786 for the Cherokee Nation, situated in present-day Western North Carolina. This creation emerged from ongoing negotiations and treaties between the United States government and Native American tribes, who were attempting to retain their traditional lands amidst the increasing encroachment by European settlers. As westward expansion gained momentum, it became clear that formalizing relationships with Native tribes was vital for both land management and political stability in the new nation.

The reservation was a product of the Treaty of Hopewell, signed in 1785, which established boundaries for the Cherokee lands and recognized their sovereignty. It marked the United States' first attempt to delineate and formally recognize Native American territories as federal reservations. However, this arrangement was fraught with complications as settlers continued to push into Cherokee land, leading to persistent conflicts and the eventual re-negotiation of treaties that often resulted in the forfeiture of land.

Over the following century, the establishment of the reservation system as a federal policy would fundamentally alter Indigenous cultures and communities, leading to significant legacy issues regarding land rights, cultural survival, and legal recognition. Although the Cherokee reservation initially offered a degree of protection, it could not prevent the flow of settler expansion that would decimate their territory and population in the long run.