The Treaty of Lewistown represented a significant moment for the Shawnee and Seneca peoples, marking a formal agreement that resulted in the exchange of their ancestral lands in Ohio for lands west of the Mississippi River. This signing captured a broader context of Native American displacement during the 19th century, as European American settlers pushed further westward, motivated by the ideology of Manifest Destiny and a desire for expansion. The roots of this agreement lay in prior treaties and pressures faced by the tribes, as the federal government sought to manage Indigenous populations amidst the country’s rapid expansion and settlement. The location of the treaty signing, Lewistown, Ohio, served as a critical environment for negotiations where tribal leaders and U.S. representatives sought compromises meant to foster cooperation while addressing the needs of the government and the Indigenous peoples involved. The terms outlined in the treaty stipulated the regions of land exchanged and emphasized the continuance of relationships despite the hardships presented by relocation.

The treaty was emblematic of the era's complexities, revealing both the attempts of Native tribes to adapt to changing circumstances and the overarching pressures applied by aggressive settlers and government policies. Though the treaty appeared a beneficial arrangement for the tribes at the moment, it was ultimately illustrative of the ongoing trend of dispossession and loss of sovereignty that Native peoples would continue to experience. The treaties often contained clauses that were later disregarded by the U.S. government, leading to further loss of land, cultural disintegration, and social upheaval among Indigenous communities. Additionally, the Lewistown treaty had repercussions for relations between various tribes as they navigated the spatial and social changes imposed by these agreements, altering alliances and traditional practices as they adapted to their new realities.

Ultimately, the Treaty of Lewistown was one of many that highlighted the precarious situation of Native nations during this period of American history. It served as a reminder of the varying degrees of agency Indigenous tribes retained in negotiations, and the often-unmet promises of protection and support from the U.S government. The long-term consequences of such treaties would lead to a series of forced migrations and a reconfiguration of Indigenous identities and territories across North America in the ensuing decades.