Located within the Gulf of Maine watershed, the Great Bay Estuary is a drowned river valley composed of high energy tidal waters, deep channels and fringing mudflats. The entire estuary extends inland from the mouth of the Piscataqua River between Kittery, Maine, and New Castle, New Hampshire through Little Bay into Great Bay proper at Furber Strait, a distance of 12 miles. The Great Bay Estuary is a tidally dominated system and is the drainage confluence of three major rivers, the Lamprey, Squamscot, and Winnicut. Four additional rivers flow into the system between Furber Strait and the open coast: the Cocheco, Salmon Falls, Bellamy, and Oyster Rivers.

The Piscataqua River is an ocean-dominated system extending from the Gulf of Maine at Portsmouth Harbor and forming the border of New Hampshire and Maine to the fork of its tributaries, the Salmon Falls and Cocheco Rivers. These rivers, several small creeks and their tributaries and ocean water from the Gulf of Maine create the Great Bay estuarine hydrosystem. The tidal range is dramatic within Great Bay. Average depth of the embayment is 2.7 m with channels extending to 17.7 m. The water surface of Great Bay covers 8.9 square miles at high tide and 4.2 square miles at low tide, leaving greater than 50% of the Bay exposed at low tide.

The Gulf of Maine is often considered by scientists and the public alike as one of the most pristine marine environments on the east coast. As a result of its water circulation patterns and the combined productivity of its seaweed, salt marsh grasses, and phytoplankton, the Gulf of Maine is also one of the world's most productive water bodies. Historically, it has been a source of livelihood for tens of thousands of commercial fishermen. More recently, recreation and tourism related employment has been recognized as a major contributor to the region's economy.