New York State Route 221 (NY 221) is a state highway in Cortland County, New York, in the United States. Its western terminus is at an intersection with NY 38 in the town of Harford. The eastern terminus is at a junction with NY 26 and NY 41 in the town of Willet. Near its western end, NY 221 intersects New York State Route 200. Together, NY 200 and NY 221 form a loop route off NY 38 between the hamlets of Harford and Harford Mills within the town of Harford. NY 221 originally followed modern NY 200 and ended at U.S. Route 11 (US 11) in Marathon when it was assigned as part of the 1930 renumbering of state highways in New York. It was extended to its present length by the following year and realigned to serve Harford later in the decade. NY 200 was assigned in the 1940s.

New York State Route 38 (NY 38) is a north–south state highway in the Finger Lakes region of New York in the United States. Its southern terminus is at an intersection with NY 96 in the town of Owego in Tioga County. The northern terminus is at a junction with NY 104A in the town of Sterling in Cayuga County. NY 38 is a two-lane local road for most of its length. The route is the main access road to parts of Auburn, Dryden, Newark Valley and Port Byron. It passes through mountainous terrain in Tioga and Cortland counties, but the terrain levels out as it heads through the Finger Lakes area and Cayuga County.