Seneca Missouri was platted by European Americans in 1869, following the American Civil War. The city was named for the Seneca Nation, one of the Six Nations of the Iroquois League, or Haudenosaunee. “This tribe was moved to the Indian Territory not many miles west of town. The word is a corruption of the Dutch word “Sinnekaas“ a term applied to them.” A post office called Seneca has been in operation since 1869.

Several houses in the rural northern Seneca area were destroyed by a tornado on May 10, 2008 in the Mid-May 2008 tornado outbreak sequence in which an EF4 tornado hit the county, killing 13 people. The Early Show broadcast their national weather report from the city on the following Monday morning. On the one year anniversary, Bill Lant, owner of Lant’s Feed and Country Store, unveiled a memorial for the people who died from the tornado. He had donated the plot of land and memorial, and had the memorial built next to his store.

The population of Seneca as of the 2010 US Census is  2,336.

The City is ran by the City Council. Council meetings are held the first and third Tuesdays of the month at 7:00pm.

The Seneca City Hall is located at 1303 Cherokee Ave.  The City has 3 office employees, 3 public works employees, and 4 police officers.