The Town of Topsham first received its legal name in the year 1717 and was incorporated in 1764, at which time the first town meeting was held (May 9, 1764). It was named after Topsham, England, because many of its founders came from that country. The Pejepscot Company was formed in 1714, when eight men purchased Richard Wharton's vast estate. Between 1717 and 1722, 33 people took up lots in Topsham. Original lots extended back two miles from the river and were said to be 25 rods wide but were found to average 26 rods. These were separated by straight lines, approximately perpendicular to the western bank of the Pejepscot River, Number One being Pleasant Point. Col. James Hunter, son of Adam Hunter, was the first white child born in Topsham (April 15, 1735). He helped build Fort Halifax in 1754, and served as an officer in the Revolutionary War.

Prior to this (approximately 1669), Thomas Gyles settled at Pleasant Point. His brother, James Gyles, settled "Up Muddy River." Thomas and Samuel York had a deed from the Sagamore Indians, dated July 20, 1670, which is now Topsham Foreside. Wharton's right was based on an Indian deed, given to him by Worumbee and five other Sagamores, dated July 7, 1684.

The first saw mill was erected on the Cathance River, in 1716. A few years later, other mills were built on the Androscoggin River, bringing much activity in manufacturing lumber between 1750 and 1770. Topsham's industries included a watch factory, pottery, nail factory, pitchfork factory, two tanneries, marble works, tobacco manufacture, two feldspar mills, and the manufacture of shingles by the use of "Kelsey's Patent Shingle Machine."

The first post office was on Main Street, opposite the "Bank" building. The postmaster was Charles R. Porter. The first known library, "The Social Library of Topsham," was founded in 1803. The Topsham Public Library opened its doors on February 7, 1931, with 1500 books on its shelves, on the first floor of the old Androscoggin Engine House on 38 Main Street. In 1941, Sarah Whitten donated her house to Topsham, it is located on Pleasant Street and known as "Whitten Memorial Library."

From Topsham to Brunswick, the only way to cross the Androscoggin River was by boat. In 1756 a toll bridge was constructed by the "Proprietors of the Androscoggin Bridge." It was destroyed by fire in 1842. The Frank J. Woods bridge was named after a farmer, for suggesting the relocation of the bridge. It took 100 men divided into crews of different categories to work on the new bridge. July 14, 1932, the old bridge was closed and torn down as the new bridge opened to the public.