This area was long occupied by indigenous peoples; in the historic period, the Mohawk people, one of the Five Nations of the Haudenosaunee, or Iroquois Confederacy, dominated this territory, ranging up to the St. Lawrence River and east to the Hudson.

They were refugees from the religious warfare along the border with France, and also had suffered the loss of crops from an extremely harsh winter in 1709, when the Rhine River froze.

In 1723, 100 Palatine families from the 1710 immigration were granted land just west of Little Falls in the Mohawk Valley under the Burnetsfield Patent.

[5] These frontier settlements were vulnerable to attack, but served as a defensive line during the French and Indian War and the American Revolution.

Developed for agriculture, the Schoharie Valley was considered a bread basket of the colony because of the amount of wheat produced even during the American Revolutionary War.

Raids led by Joseph Brant and his Iroquois allies destroyed most of the buildings in the town of Schoharie.

Cheesemaking and the dairy industry were important in the 19th century, when products were sold to New York City.

Schoharie Creek rose to record levels, resulting in massive destruction of roads, homes, and businesses within the Town.

Due to the devastation of what was classified as a 500-year flood, federal agencies such as FEMA and the National Guard were called in to assess damages and provide relief, shelter and assistance to affected residents.

Many farms in the area suffered severe economic losses due to animals lost or drowned in flood waters, barns deemed unusable, and fall harvest crops ruined.

Part of the northeast town line forms the border of Schenectady County.