Preble is on the north border of Cortland County and is north of the city of Cortland.
Preble is within the former Central New York Military Tract. The land was first settled around 1796.
The town of Preble was organized in 1808, the year Cortland County was formed, from the town of Tully (now in Onondaga County). Preble was one of the original towns of the county when it was formed. The town was reduced in size by the later formation of the town of Scott.
In 1865, the town's population was 1,267.