European colonists settled the Town of Arlington in 1635 as a village within the boundaries of Cambridge, Massachusetts, under the name Menotomy, an Algonquian word considered by some to mean "swift running water", though linguistic anthropologists dispute that translation. A larger area was incorporated on February 27, 1807 as West Cambridge, replacing Menotomy. This includes the town of Belmont, and outwards to the shore of the Mystic River, which had previously been part of Charlestown. The town was renamed Arlington on April 30, 1867 in honor of those buried in Arlington National Cemetery.

The Massachusett tribe lived around the Mystic Lakes, the Mystic River, and Alewife Brook. Chief Nanepashemet was killed by a rival tribe in about 1619, and Nanepashemet's widow "Squaw Sachem of Mistick" became the acknowledged leader of the tribe. In 1639, she deeded the land of what was then Cambridge and Watertown to the colonists. She lived her last years on the west side of the Mystic Lakes near Medford, where she died sometime between 1650 and 1667