Settled in 1628 by Thomas Purchase and other fishermen, the area was called by its Indian name, Pejepscot, meaning "the long, rocky rapids part [of the river]." In 1639, Purchase placed his settlement under protection of the Massachusetts Bay Colony. During King Philip's War, Pejepscot in 1676 was burned and abandoned, although a garrison called Fort Andros was built on the ruins during King William's War. The Treaty of Portsmouth of 1713 then brought peace to the region between the Abenaki Indians and English settlements. ^[1]

In 1714, a consortium from Boston and Portsmouth bought the land, thereafter called the Pejepscot Purchase. The Massachusetts General Court constituted the township in 1717, naming it Brunswick in honor of the House of Brunswick and its scion, King George I. A stone fort called Fort George was built in 1715 near the falls. But on July 13, 1722, warriors from Norridgewock burned the village. Consequently, Governor Samuel Shute declared war on the Abenakis. In 1724, 208 English troops left Fort Richmond and sacked Norridgewock during Dummer's War. Brunswick was again rebuilt in 1727, and in 1738 incorporated a town. It became a prosperous seaport, where Bowdoin College would be chartered in 1794.^[2]

The Androscoggin River falls in 3 successive stages over a distance of 41 feet, providing water power for industry. Brunswick became a major producer of lumber, with as many as 25 sawmills. Some of the lumber went into shipbuilding. Other firms produced paper, soap, flour, marble and granite work, carriages and harness, plows, furniture, shoes and confections. The town was site of the first cotton mill in Maine, the Brunswick Cotton Manufactory Company, built in 1809 to make yarn. Purchased in 1812, the mill was enlarged by the Maine Cotton & Woolen Factory Company. In 1857, the Cabot Manufacturing Company was established to make cotton textiles. It bought the failed Warumbo Manufacturing Company and expanded the brick factory along the falls. Needing even more room, the company in 1890 persuaded the town to move Maine Street.

Brunswick today has a number of historic districts recognized on the National Register of Historic Places, including the Pennellville Historic District, to preserve shipbuilders' and sea captains' mansions built in the Federal, Greek Revival and Italianate architectural styles. Principal employers for Brunswick include Naval Air Station Brunswick, L.L. Bean, Bath Iron Works, as well as companies that produce fiberglass construction material and electrical switches. A number of health services providers serving Maine's mid-coast area are located in Brunswick.

The book Uncle Tom's Cabin was written by Harriet Beecher Stowe while she was living in Brunswick because her husband was a professor at Bowdoin. She got a key vision for the book in the First Parish Church. A scene in the 1993 movie The Man Without a Face was filmed in the town.