NY 220 begins at an intersection with NY 41 north of the hamlet of Smithville Flats in the Chenango County town of Smithville. It heads to the northeast, paralleling a small creek as it progresses through the rural town consisting mostly of cultivated fields. NY 220 passes into the town of McDonough and enters a hamlet bearing the same name, where it turns eastward. The route winds its way through the eastern, forested portion of the town to the small community of East McDonough, located near the McDonough–Preston town line. Here, NY 220 turns southeast at Steere Road (unsigned NY 991A) and continues into Preston. Where NY 991A heads north to serve Bowman Lake State Park.