New York State Route 281 (NY 281) is a north–south state highway in central New York in the United States. It extends for 16.56 miles (26.65 km) across Cortland and Onondaga counties. The southern terminus of the route is at an intersection with NY 13 in the town of Cortlandville. Its northern terminus is at a junction with U.S. Route 11 and NY 80 near the village of Tully. NY 281 meets NY 90 in the village of Homer and connects to Interstate 81 twice. The route parallels I-81 for all but the southernmost 2.5 miles (4.0 km) of its routing.