The homeland of both the Seneca and Cayugas originated in what is today the upstate Finger Lakes Region of the state of New York. The Seneca are the western-most members of the League of the Iroquois (Six Nations) know as the "Keepers of the West Door" while the Cayuga located to the east of the Seneca and are referred to as "Younger Brothers" within the League of Six Nations. Also known collectively as "Mingo" or as "Seneca," they are the ancestors of today's Seneca-Cayuga Tribe of Oklahoma.

In 1817 the United States established two reservations for the Ohio Iroquois "Senecas." One was for the Seneca of Sandusky, a mingling of Cayuga, Seneca, Onondaga, Mohawk, Erie, Conestoga and others, along the Sandusky River and the second was for a consolidated band of Seneca and Shawnee at Lewistown. Both groups exchanged their Ohio reserves for adjoining land in the Indian Territory in 1831.

Approximately 358 Seneca of Sandusky arrived in Oklahoma in the summer of 1832. About 258 members of the Mixed Band of Seneca and Shawnee arrived later that year. Following negotiations with the Stokes Commission in December 1832, the Tribes readjusted their reservation boundaries and joined together as "the United Nation of Senecas and Shawnees." Most Seneca and Shawnee spent the Civil War years as refugees in Kansas. The U.S. government separated the Seneca from the Shawnee in 1867. The Sandusky and Mixed Band Seneca were organized as a single Seneca tribe and the Shawnees became the Eastern Shawnee. Both surrendered land that was later occupied by Peoria, Piankashaw and other Indians.

During the 1840s, 1870s and early 1880s, the Seneca received newcomers, including Cayuga, Mohawk and Seneca proper, from Canada and New York and had a population of roughly 255 in 1890. The Seneca Reservation was first allotted to 130 individuals in 1888; by 1902 a total of 372 allotments had been issued. Today the Seneca-Cayugas continue their rituals as well as ceremonial calendar and dances such as the Green Corn Ceremony and during this annual ceremony, the Peach Seed game and a ritual football game continue to be played. Oklahoma tribal members continue to interact with their New York and Canadian kinfolk as well as with neighboring northeastern Oklahoma Tribes for ceremonies, athletic contests and powwows. The primary language of the Seneca-Cayuga Tribe is Cayuga of which the Seneca language is closely related.