It runs just over 13 miles (21 km) from one section of the Pennsylvania state line to another, passing through two small hamlets and providing the Southern Tier Expressway (I-86/NY 17) with its westernmost exit in New York.

The route heads north through rural southwestern Chautauqua County to the small community known as Cutting, where it overlaps NY 474 for a tenth of a mile (0.16 km) westward before resuming its trek northward.

[3] Roughly 1.5 miles (2.4 km) north of Cutting, NY 426 veers to the west to avoid a large ridge situated near Beaver Meadow Brook, a small stream leading to French Creek.

Past the expressway, NY 426 continues northwest for another 2 miles (3.2 km) through nondescript terrain to the Pennsylvania state line, where it becomes the northern segment of PA 426.

[3] The entirety of NY 426 was assigned as part of the 1930 renumbering of state highways in New York as a northward extension of PA 189, a short route leading south to Corry, Pennsylvania.