NY 281 proceeds northward through Homer, now with the name of South West Street, entering the village of Homer. The route passes east of Glenwood Cemetery, intersecting with NY 90 (Cayuga Street). NY 281 continues north through Homer, remaining a two-lane residential road. Near Grove Street, the route changes monikers to North West Street, crossing through a dense stretch of residences. After turning northeast, NY 281 intersects at-grade with NY 41 (Clinton Street), before continuing to Stanford Drive, which marks the end of the village of Homer. Back in the town of Homer, the route proceeds northeast through a rural stretch of Cortland County, winding northeast into a parallel with I-81.