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The League of the Iroquois, also known as the Longhouse or the Five Nations (later Six Nations with the Tuscaroras in 1722), was a powerful alliance of Native nations in upstate New York. Though they didn’t live in the Appalachian region, they influenced it heavily.
Founded before European contact, the Iroquois traded with both the French and British and dominated other Native groups like the Lenape, claiming territory including parts of present-day West Virginia. This helped them remain independent through the 1600s and 1700s.
While the Iroquois only hunted in this region, Virginians eventually bought land rights from the both the Iroquois and Cherokee. However, Shawnees, Delawares, and other Indians resisted settlers. After the American Revolution, Iroquois power faded, leaving only a small Seneca reservation and the Shawnees to continue to resist alone.