PA 88 begins as Main Street then turns to the west crossing the Monongahela River into Greene County on the Albert Gallatin Memorial Bridge.

In the boro of Carmichaels, PA 88 is called Vine Street and crosses Muddy Creek.

In Jefferson Township, PA 88 intersects the eastern terminus of Pennsylvania Route 188 southwest of Rices Landing.

After crossing the Tenmile Creek, PA 88 has entered Washington County as Front Street.

As PA 88 begins to shift to the east, it enters the following boros: Elco, Roscoe, and Stockdale.

In Carroll Township, PA 88 is called Country Club Road and meets the southern terminus of Pennsylvania Route 837.

Then PA 88/PA 136/PA 837 become Main Street and intersect the northern terminus of Pennsylvania Route 481.

Then PA 88 re-enters Union Township passing several businesses and then becomes Library Road near the Allegheny County line.

The entire 8.5-mile (13.7 km) Allegheny County stretch of PA 88 is also designated as Library Road.

PA 88 originally was planned to extend from Pittsburgh all the way north to Erie, along the highway that now largely follows US 19.

[5] The Pittsburgh-to-New Castle section was largely split off on July 15, 1960 to form Pennsylvania Route 65, in honor of the 65th Infantry Division of the United States Army during World War II.

This designation change was made to reduce the number of concurrent routes in Pittsburgh.