Tonawanda Reservation (also known as the Tonawanda Creek Reservation is located in a remote area of western NY, a few miles north of the New York State Thruway. Although most of the reservation lies in Genesee County, portions are within the boundaries of Erie and Niagara counties. The Tonawanda Creek flows through the entire reservation to the Niagara River, separating the part in Niagara County from the parts in Erie and Genesee counties. The northern boundary of the reservation's Niagara County portion is part of the Tonawanda Wildlife Management Area.

Anthropologist Lewis H. Morgan worked with the Tonawanda Seneca during the mid 19^th century to learn about  Iroquois kinship and social structures. In 1851 he published  The League of the Ho-de-no-sau-nee or Iroquois, a book that has  influenced much subsequent anthropological research. Much of the information was provided by his colleague and friend Ely S. Parker, a Seneca born on the reservation in 1828. Morgan dedicated his book to Parker and credited him with their joint research.

The 2000 census recorded a population of 533 people residing on the reservation. Currently, it has more than a half dozen businesses located on Bloomingdale Road within the reservation. Several sell untaxed, low-price cigarettes and gasoline. Other businesses sell Seneca craft goods, groceries, and prepared food.

Tonawanda has maintained a hereditary system of government with 10 chiefs. They elect a chairman, treasurer, and clerk. Agreements are made with New York State to maintain the roads and they contract with local towns to provide fire and ambulance services.