Penn Avenue is a major arterial street in Pittsburgh and Wilkinsburg, in Pennsylvania.

Exiting downtown it is the major route through the city's Strip District, Lawrenceville, Bloomfield, Garfield and East Liberty neighborhoods.

Its eastern portion exits the city at Wilkinsburg where it continues to exist as Penn Avenue with a numbering system that begins anew using small numbers as it approaches Interstate 376 the "Parkway East".

The road passed through a tiny settlement which grew to become Greensburg, Pa.

In early 2014, the City of Pittsburgh announced the installation of the first set of protected bike lanes in the area.