Pennsylvania is divided into more than a dozen distinct physiographic regions, most of which extend in curved bands from east to south. Beginning in the southeast, the first region (including Philadelphia) is a narrow belt of coastal plain along the lower Delaware River.. The next region is the Piedmont Plateau, a wide area of rolling hills and lowlands. The Great Valley , runs from the middle of the state's eastern border to the middle of its southern border. The eastern, central, and western parts of the Great Valley are known as the Lehigh, Lebanon, and Cumberland valleys, respectively. West and north of the Great Valley, the Pocono Plateau rises to about 2,200 ft (700 m).

The northern part of the state comprises of the Allegheny High Platea and the Appalachian Plateaus. , The southwestern extension of the Allegheny High Plateau contains the state's highest peak, Mt. Davis, at 3,213 ft (980 m). A narrow lowland region, the Erie Plain, borders Lake Erie in the extreme northwestern part of the state.

The largest natural lake within the state's borders is Conneaut Lake, about 30 mi (48 km) south of the city of Erie, with an area of less than 1.5 sq mi (39 sq km). The largest manmade lake is Lake Wallenpaupack, in the Poconos, occupying about 9 sq mi (23 sq km). Pennsylvania claims more than 21 sq mi (54 sq km) of the Pymatuning Reservoir on the Ohio border.

The most important river is the Susquehanna River and its tributaries drain more than 46% of the area of Pennsylvania, much of it in the Appalachian Mountains. The Delaware River forms Pennsylvania's eastern border and, like the Susquehanna, flows southeastward to the Atlantic Ocean. Most of the western part of the state is drained by the Allegheny and Monongahela rivers, which join at Pittsburgh to form the Ohio. The Beaver, Clarion, and Youghiogheny rivers are also important parts of this system..