Otisco Lake's name may have been derived from the Iroquois name for the lake's outlet, Nine Mile Creek, Us-te-ke, meaning "bitter-nut-hickory". At least one older map, published in 1825, has the name spelled as "Ostisco".[2] The name may also have been derived from the word ostickney, meaning "waters much dried away", or from the Onondaga word ostick, meaning "the water is low".[3]