Native Americans were the first to live on the shores of Great Bay. They survived on the abundant fish, shellfish, waterfowl and mammals that lived in and around the estuary.

The early 1600s brought the arrival of European settlers who also took advantage of the seemingly endless supply of resources. They used the Bay to transport their harvests. The tidal influence was the perfect way to move goods without much human or animal effort. A simple, flat-bottomed boat, the Gundalow, was developed to make use of the tides and carry heavy loads in shallow waters.

Gundalows transported many types of freight. Saltmarsh hay, lumber, fish, clay and textiles were just a few of the cargos. Salt hay harvested along the shores was used as food and bedding for horses and cattle. Sawmills located along the tidal rivers produced lumber that was exported to other US ports. The lumber produced also fueled the shipbuilding business along the Piscataqua River until steam-powered steel vessels became cheaper to build. Brickyards also dotted the shores of Great Bay and its tributaries. Blue marine clay was harvested from along the estuary shores and made into bricks that were used to build locally and all around New England. Cotton mills were an important part of the Industrial Revolution. Wherever gundalow ports were, mills were built.

In 1835, the Boston and Maine railroad made its debut in New Hampshire and essentially took the place of gundalows. Speed and year round operation made the rails the choice for shipping cargo.

Today, Great Bay is enjoyed for the recreation, education and research opportunities it offers.