Annisquam Lighthouse is situated on the Annisquam River, which is in fact an estuary that connects Ipswich Bay to Gloucester Harbor. In 1631, the village of Annisquam was founded on the eastern side of the northern end of the river. The village grew into a fishing and shipbuilding center that during its heyday rivaled Gloucester. For ships traveling the coast, the river was considered an important refuge.

The lighthouse got its start with an April 29, 1800 act of Congress to erect a light on Wigwam Point in Annisquam. The act also provided for the appointment of a keeper and other support of such lighthouse at the expense of the United States, provided that sufficient land for the lighthouse be granted to the United States. That land was to come from Gustavus Griffin, who deeded six and one half acres on October 26, 1800, for which the U.S. Government paid him $140. The area was known as Wigwam Point, because it was historically a summer gathering place for Native Americans. Annisquam is a combination of the local Native Indian name for a harbor, “squam”, and “Ann” from Cape Ann, after Queen Anne of England. Originally, it was frequently written as “Anesquam”.