Plentiful game, the marshes and lush river-fed vegetation, and an abundance of fish supported the northeast Native American people who were present in the region for thousands of years until English settlers displaced them in the early 17th century.

The Squamscott begins at downtown Exeter and runs north between Newfields and Stratham to Great Bay, which is connected to the Piscataqua River, and eventually feeds into the Atlantic Ocean.

After rising at the Great Bridge (a Works Progress Administration project that carries what is now New Hampshire Route 27) in downtown Exeter, the river passes the Phillips Exeter Academy boathouse, then tends north alongside the Swasey Parkway, through the haymarshes, passing by the town's water purification plant and then under Route 101, a major east–west arterial road in New Hampshire.

Fish species include brook trout, small and large mouth bass, yellow perch, and chain pickerel; there is also a spawning area for alewife and blueback herring.

These sewers serve approximately 35% of the town including Jady Hill, Exeter Mill and sections of the commercial areas on Portsmouth Avenue, and were discovered by cleaners to be corroded from being over fifty years old.