NY 281 begins at an intersection with NY 13 (Tompkins Street) in the town of Cortlandville next to the Walden Oaks Country Club. NY 281 proceeds north on West Road, a four-lane commercial street through Cortlandville, soon intersecting with County Route 120 (CR 120; McLean Road). Retaining the commercial design, NY 281 crosses over a railroad line, passing west of State University of New York at Cortland. The route continues northeast, passing east of Cortland County–Chase Field Airport. At Luker Road, NY 281 becomes a four-lane commercial boulevard again, entering an at-grade interchange with NY 222 and soon an intersection with CR 111 (Kinney Gulf Road).