Route 21 is a 99.99 (literally) mile long state highway that runs north/south from Route 104 (Ridge Road East) in Williamson to Route 417 in Andover. Route 21 passes through Manchester, Canandaigua, Naples and Hornell. Route 21 intersects many major east-west routes, including the Thruway in Manchester, Route 5 and 20 in Canandaigua, and the Southern Tier Expressway near Hornell.
Route 21 goes nearly straight south until it gets to Atlanta south of Naples, at which point it turns west. At Wayland, it makes a 90 degree turn back south. It stays generally southern direction for the rest of it's journey.