Gilsland Farm and the surrounding shorelands have a long history of human use. For thousands of years they were home to the Wabanakis and their ancestors. It was an ideal spot: the estuary's vast tidal flats provided a rich source of shellfish and attracted huge concentrations of shorebirds, the sheltered waters of Casco Bay offered superb fishing and hunting for waterfowl and marine mammals, and the river provided an important travel route to the interior.
The arrival of English settlers in the 1630s signaled the end of this era and the beginning of a new one. Claiming and dividing the land into individual properties, the settlers soon cut the timber from the shorelands and established farms. Along the Presumpscot, which means "many rough places," they erected gristmills and sawmills. In the mid-1800s, Silas Noyes bought the site of what would become Gilsland Farm and built the red wood-frame house still standing near the entrance to the sanctuary.