Archaeological studies of the Lamprey have shown that human presence along the river dates back more than 8600 years. Indigenous peoples were the original “summer people”, living inland in the winter and traveling to the Great Bay Estuary in summer. The people were probably from the Piscataqua or Squamscot tribes. They called themselves the Abenaki, or People of the Dawn, and belonged to the larger Algonquin group. The Lamprey, with its strong geographic connection to Great Bay, was a logical place to establish camps. The estuary provided abundant fish, shellfish, and water foul; all easily transported to camps via canoes on the river.
Early encounters with pre-colonial visitors from Europe often proved fatal for the indigenous populations. The diseases brought by European hunters and traders took a heavy toll on people who lacked immunity. When colonists arrived to settle the land in 1623, the population of local peoples had already been reduced significantly.
Initially, relations between indigenous and European peoples were friendly and based on trade. As more colonists arrived and shaped the land and relationships to meet their needs, conflicts grew between the two groups. By 1672, most indigenous peoples had left the area and had moved to the Hudson River, near what would become Troy, New York.
The New Hampshire Division of Historical resources considers the Lamprey's riverbanks to be archaeologically sensitive and to have a strong potential to possess previously unidentified sites that were used by indigenous peoples.