The Treaty of Greenville was signed as a pivotal agreement following the series of conflicts known as the Northwest Indian War, which erupted in the 1790s over control of the lands in the Ohio Country. This war involved the U.S. military against a coalition of Native American tribes who sought to resist encroachment on their ancestral territories. The treaty was negotiated at Fort Greenville, in present-day Ohio, following the U.S. victory at the Battle of Fallen Timbers in 1794. With the pressure of military defeat looming, tribal leaders convened to negotiate terms aiming to secure their remaining lands and establish a degree of sovereignty.

The treaty was significant not only for the cessation of hostilities, but also for its terms, which recognized the Miami River region as a boundary while ceding much of present-day Ohio to the United States. Notable leaders from various tribes, such as Shawnee Chief Tecumseh, participated in the negotiations. Although Tecumseh was not present at the signing, his future resistance to U.S. expansion was a direct result of the agreements made in Greenville. The treaty also paved the way for increased settlement by American pioneers in the region, leading to a dramatic shift in land ownership and usage.

In the broader context of American history, the Treaty of Greenville established a framework for future treaties between the U.S. government and Native American tribes. It laid the groundwork for subsequent interactions and conflicts that would shape the Westward Expansion era. Despite its initial promises, the treaty would later become a source of contention as more settlers moved into Ohio and beyond, disregarding the established boundaries, driving further displacements of Native peoples.