NY 66 begins at an intersection with US 9 and NY 23B (Green Street) in the center of the city of Hudson. Proceeding northeast along Union Turnpike, NY 66 becomes a two-lane city road through Hudson, soon leaving for the town of Greenport, where it becomes a two-lane commercial street north of the city. Retaining its northeastern direction, the route crosses over the Claverack Creek and enters the town of the same name. The route passes the Dutch Village mobile home park and several residences before reaching an intersection with County Route 18 (CR 18 or Fish and Game Road). After CR 18, NY 66 becomes primarily rural in nature.