Otisco is a town in Onondaga County, New York, United States. The population was 2,541 at the 2010 census. Otisco is in the southwest part of the county, situated at the northern edge of the Appalachian Highlands, where an escarpment declines to the Lake Ontario plain and the city of Syracuse five miles to the north. Extremely hilly terrain affords a sense of spatial grandeur and magnificent views.