[5] Seneca grew up along the wagon route from St. Joseph, Missouri to Oregon and California.

British explorer Richard Francis Burton en route to California in 1860 passed through town and noted: "... Seneca, a city consisting of a few shanties ..."[6] Seneca was a station on the Pony Express of the early 1860s.

The Seneca team played the 1910 season as members of the Class D level Eastern Kansas League, finishing in 2nd place.

[9] According to the United States Census Bureau, the city has a total area of 1.63 square miles (4.22 km2), all land.

There were 982 housing units at an average density of 602.5 per square mile (232.6/km2).

40.5% of all households were made up of individuals, and 22.7% had someone living alone who was 65 years of age or older.

36.9% of all households were made up of individuals, and 23.4% had someone living alone who was 65 years of age or older.

The community is served by Nemaha Central USD 115 public school district.