From the Ohio border, the Pennsylvania Turnpike carries I-76 into and across most of Pennsylvania, bypassing all major cities - Youngstown to the south, Pittsburgh to the north and Harrisburg to the south.
At Valley Forge, northwest of Philadelphia, I-76 leaves the Turnpike to run into Philadelphia on the Schuylkill Expressway, while Interstate 276 continues east on the Turnpike. Immediately after exiting, I-76 interchanges with the U.S. Route 202 and U.S. Route 422 freeways, and then crosses Interstate 476 and begins running along the southwest shore of the Schuylkill River. Interchanges provide access to the Roosevelt Expressway (U.S. Route 1) and Vine Street Expressway (Interstate 676); the latter runs through downtown Philadelphia while I-76 bypasses to the south.
The last interchange before the Walt Whitman Bridge over the Delaware River into New Jersey is with Interstate 95. Some of the ramps involve traffic signals, as the ramps to I-95 were retrofitted into an existing interchange when I-95 was built, and the toll booth for the bridge lies west of the crossing of the two roads.