PA 426 begins at an intersection with PA 27 west of Pittsfield and north of Garland in Pittsfield Township. The route heads northwest through rural Warren County, intersecting Old PA 77 (also formerly known as PA 277) at Spring Creek on its way to the Erie County line and the city of Corry beyond. PA 426, now East Main Street, proceeds west through southern Corry to an intersection with PA 77 (West Main Street) at Center Street. PA 426 turns north onto Center, crossing over a set of railroad tracks immediately north of the junction with PA 77 and passing through northern Corry prior to meeting U.S. Route 6 near the northern city line. Outside of Corry, PA 426 becomes Hare Creek Road, named for the waterway that PA 426 parallels into New York, where it becomes NY 426.
At the opposite end of NY 426, the route re-enters Pennsylvania as the northern segment of PA 426. Like most of the areas surrounding the southern segment of PA 426, most of the northern portion is as equally rural. Other than the two routes at its termini, the northern PA 426 does not intersect any signed routes along its length. The route heads northwest, then west from the state line as Findley Lake Road. In the area surrounding the borough of North East, PA 426 passes under Interstate 90 prior to terminating at PA 89 near the southern edge of the borough.
By 1950, the route was commissioned along where it mostly runs today. The only exception was the southernmost segment of PA 426, which was still designated as PA 77 from Spring Creek to Garland.[4]
By 1980, the southernmost section was redesignated from PA 77.[5]
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