When NY 280 was originally assigned as part of the 1930 renumbering of state highways in New York, it was little more than a short spur route off of NY 17 that followed the Allegheny River south to the hamlet of Quaker Bridge. In 1965, the Kinzua Dam was completed, leading to the creation of the Allegheny Reservoir and the inundation of much of NY 280. As a result, the route was shifted onto a new alignment that was constructed along the eastern edge of the reservoir.