Now paralleling a railroad line, NY 281 intersects with CR 106 (Song Lake Crossing Road). Soon after intersecting with CR 106A (Tully Center Road), NY 281 turns northwest, crossing the county line into Onondaga County. Right at the county line, NY 281 intersects with CR 257 (Marybelle Road), now in the town of Tully. The route bends northward, intersecting with CR 134 (Meeting House Road) as a two-lane rural road. A short distance to the north, I-81's exit 14 intersects with NY 281, which serves as a frontage road to an intersection with NY 80 and US 11. This intersection serves as the northern terminus of NY 281, while the right-of-way continues north as US 11.