U.S. Route 19 in Pennsylvania closely parallels Interstate 79 for its entire length. US 19 enters Pennsylvania in Greene County near Mount Morris. Its northern terminus is in the city of Erie. Part is named for Commodore Oliver Hazard Perry, hero of the Battle of Lake Erie.

In northern Washington County, U.S. Route 19 was modernized after the former Pittsburgh Railways Interurban (PRCo) trolley service was discontinued in August 1953. Initially Route 19 ran parallel to the trolley line, and later expanded over the tracks through part of Mt. Lebanon in southern Allegheny County.

US 19 then proceeds north through Pittsburgh's Northside, West View, Perrysville and Ross Township, McCandless Township and Wexford, where it is referred to as Perry Highway. In Cranberry Township, it connects with I-79, the Pennsylvania Turnpike, and PA 228. Continuing through Mercer and Crawford counties, the route terminates in the city of Erie.

A Truck 19 designation exists in Pittsburgh, running from Wexford, Pennsylvania to Mt. Lebanon, Pennsylvania. Although both of that route's termini are with the regular U.S. 19, the two routes also intersect near the Fort Pitt Tunnel on Pittsburgh's West End.