NY 222 begins at an intersection with NY 38 (Main and Cayuga streets) in the village of Groton. The route proceeds east along the two-lane East Cortland Street, serving several blocks of homes in the eastern part of the village. It soon exits the village limits, at which point NY 222 changes names to Cortland Road and the residential areas give way to wide stretches of farmland. As the highway runs across the town of Groton, it passes only a handful of houses as it intersects County Route 102 (CR 102, named Salt Road) and CR 103A (Champlin Road) at junctions roughly apart. NY 222's eastward track continues to a nearby intersection with CR 180 (Lafayette Road), where the route crosses Fall Creek and darts northeastward to run along the base of a large hill.