It rises at Great East Lake, Newichawannock Canal, and Horn Pond and flows south-southeast for approximately 38 miles (61 km), forming the border between York County, Maine, and Strafford County, New Hampshire.

[2] It provides hydroelectric power at the New Hampshire towns of Milton, North Rochester, East Rochester, New Hampshire, Somersworth, and Rollinsford, and in Maine at Berwick and South Berwick.

The final three miles of the river, from South Berwick to the Piscataqua, are tidal.

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