The county's name comes from the Seneca Nation of the Haudenosaunee (Iroquois), who occupied part of the region.

This was an enormous county, including the northern part of New York as well as all of the present state of Vermont and, in theory, extending westward to the Pacific Ocean.

In the fall of 1779 on orders from commander-in-chief General George Washington the Sullivan Expedition conducted a scorched earth campaign against the Iroquois who sided with the Loyalists in the Revolutionary War.

In 1784, following the peace treaty that ended the American Revolutionary War, the name of Tryon County was changed to Montgomery County in honor of the general, Richard Montgomery, who had captured several places in Canada and died attempting to capture the city of Quebec, replacing the name of the hated British governor.

Part of this territory, the current towns of Covert and Lodi, were returned to Seneca County in 1819.

It included the constitution of two county courts and jury districts under Chapter 137 of the New York State Laws of 1822.

[3][4] In 1895, the Seneca County Board of Supervisors voted to abolish the setup of two jury districts.

[4] At least once a year, the County Board of Supervisors holds its monthly meeting in Ovid to maintain the two-shire status.

On April 6, 1830, the Church of Jesus Christ of Latter Day Saints was founded in Seneca County.

The event took place at the log home of a local farmer, Peter Whitmer.

Although church headquarters moved out of the area shortly thereafter, a historical visitor’s center is still operated at that location.

Both the New York State Thruway and the Erie Canal cross the northern part of the county.

The former Willard Drug Treatment Center and Five Points Correctional Facility are two New York State prisons located in the county.

[16][17] The board normally meets every 2nd Tuesday of the month at the Seneca County Office Building in Waterloo with at least one meeting per year held at the old Seneca County Courthouse Complex in Ovid as honor of the two-shire system.

With the exception of 2000 and 2020, when Al Gore and Donald Trump, respectively, carried the county, voters here have opted for the winner of every Presidential election since 1980.