The West Branch Susquehanna River is one of the two principal branches, along with the North Branch, of the Susquehanna River in the northeastern United States. The North Branch, which rises in upstate New York, is generally regarded as the extension of the main branch, with the shorter West Branch being its principal tributary.

The West Branch, which is 243 miles (391 km) long, is entirely within the state of Pennsylvania, draining a large mountainous area within the Allegheny Plateau in the western part of the state. Along most of its course it meanders along mountain ridges and through water gaps, forming a large zigzag arc through central Pennsylvania around the north end of the Allegheny Ridge. In colonial times the river provided an important water route to the Ohio River valley. In the 18th century, its lower valley became a significant industrial heartland of Pennsylvania.

The West Branch rises on the west side of the Alleghenies in northwestern Cambria County, approximately 20 miles (32 km) east of the city of Indiana. It flows generally north, crossing the eastern corner of Indiana County at Cherry Tree, then into southern Clearfield County.  In northern Clinton County it turns to the southeast to Lock Haven. At Lock Haven it turns east, flowing through the West Branch Susquehanna Valley along the foot of Bald Eagle Mountain ridge past Williamsport, the largest city on the river, then turns south at the end of the ridge.

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