Groton had its precarious beginnings when John Tinker followed Indian Trails from the Bay area and settled near the mouth of Nod Brook on the Nashua to set up his trading post to do business with the Nashaway Indians. The area was known as Petapawag, an Indian name for swampy land. Adventuresome families soon followed, on foot or on horseback, and found it a good place for the necessary farming and fishing.

In 1655, this trading post evolved into a formal settlement called The Plantation of Groton, which encompassed all of what is now Groton and Ayer, nearly all of Pepperell and Shirley, a large part of Dunstable and Littleton, as well as smaller parts of Harvard, Westford, Nashua, NH, and Hollis, NH. It was named in honor of one of the original Selectmen, Dean Winthrop, who was born in Groton, Suffolk County, England.

In 1676, during the King Philip's War, Indians attacked the town and burned down all but four garrison houses. The surviving residents fled to Concord and other safe havens returning two years later to rebuild the town.

As Groton's population grew so did many supporting industries including a soapstone quarry, a large hop-growing industry, a brick factory, a saw mill, a grist mill, and a pewter mill which produced tea pots, plates, cups, and buttons.

West Groton lies within a "V" formed by the Nashua and the Squannacook rivers. The old red brick Groton Leatherboard factory still stands on the Squannacook River as an example of the late industrial period of a New England mill village. West Groton has its own post office, fire station, and water department. In the past, other areas of Groton were designated as east, south, and north, but only West Groton's name survived.

The Lost Lake area was created at the turn of the century through damming nearby streams and flooding an existing field. It was popular as a summer resort for city residents and today both permanent and summer residents live there.