The Treaty of Greenville was signed August 3, 1795, between the United States, represented by Gen. Anthony Wayne, and chiefs of the Indian tribes located in the Northwest Territory, including the Wyandots, Delawares, Shawnees, Ottawas, Miamis, and others. The negotiations took place at Fort Greenville on the southwestern branch of the Miami River where Greenville, Ohio, is now located. The treaty brought to an end a series of hostilities along the Ohio Valley frontier in the early 1790s which had culminated in Wayne's victory over the tribes at the Battle of Fallen Timbers, August 20, 1794. The battle and treaty were significant for the settlers of Western Virginia because they brought peace and a final end to the Indian wars in this part of the country.

Under the terms of the treaty, the Indians ceded to the United States about two-thirds of present Ohio. Prisoners held by the tribes were to be released within 90 days, and the U.S. was allowed to maintain portage sites and trade centers at places including Detroit, Michilimackinac, and the future location of Chicago. The Indians received an immediate payment of $20,000 in goods and an annual payment thereafter of $9,500 in goods. In addition, the Indians were given the right to hunt in the territorial cession and the authority to drive off or punish settlers of European descent who infringed on their lands. The treaty did, however, prohibit "private revenge or retaliation" and provided instead for a mediation process.

While the treaty officially brought peace to the Ohio Valley frontier, problems continued because whites almost immediately began to breach the Indian territory to the west. Furthermore, some tribal leaders, such as Tecumseh, had not signed the treaty and did not recognize its provisions. Western Virginia settlers, however, were henceforth safe from Indian attack.