In October 1960, ground was broken on the Kinzua Dam, which would dam the Allegheny River downriver from NY 280 at a point east of Warren, Pennsylvania. The structure was completed on December 13, 1965, leading to the creation of the Allegheny Reservoir. Much of NY 280 was inundated by the new reservoir, as were Cold Spring, Quaker Bridge, and a significant portion of Pennsylvania Route 346 (PA 346) that ran along the river in Warren County. As a result, new alignments were built for both NY 280 and PA 346 along the eastern edge of the new reservoir. Construction of NY 280's new alignment began in 1965 and was completed by 1968. NY 280 now began at the realigned PA 346 at the state line and ended at exit 18 of the Southern Tier Expressway, which was built between Steamburg and Salamanca during the mid-1960s.