The approximate date of the first settlement of Falmouth was 1632, by Arthur Mackworth, on what is currently known as Mackworth Island. In 1658, the town was incorporated as the seventh town in Maine, with an area covering the current towns of Portland, South Portland, Cape Elizabeth, and Westbrook.
In 1700, the New Casco Fort and an adjoining trading post was constructed, and in 1703, the fort was attacked by French soldiers supplemented by Native Americans with whom they were allied. The fort was demolished by order of the Governor of Massachusetts in 1716, the area of Maine then being controlled by Massachusetts.
Cape Elizabeth was set off from Falmouth in 1765, including the area that is now South Portland. Portland became a separate municipality in 1786, and Westbrook broke away in 1814, although the boundaries between Falmouth and Westbrook were readjusted several times during the 19th century. Mackworth Island was donated to the state in 1943, and is now an animal and bird sanctuary, as well as the site of a state school for the deaf.