The highway briefly parallels Fall Creek; however, it soon splits to the southeast at a junction with CR 103 (Groton City Road). From here, NY 222 continues on a generally southeasterly alignment along the base of a rural valley to the Tompkins–Cortland county line. Now in the town of Cortlandville, the route loses the Cortland Road name as it curves eastward to match similar turns in the course of the valley. The highway follows a winding course until the surrounding gully empties into the much wider Tioughnioga River valley, where the route straightens out and intersects with CR 119 (Sears Road). East of this point, NY 222 begins to run northeastward past homes as it approaches Cortland County–Chase Field Airport. The route provides direct access to the airport and subsequently meets NY 281 (West Road) at the northeastern tip of the airport property.