The town was also the location of a Praying Indian village, one of many throughout the Massachusetts colony, called Nashoba Plantation, on the land between Lake Nagog and Fort Pond, and settled mostly by the local Nipmuc tribe from 1643 until the time of King Phillip's War. During this war, the Indians were rounded up and sent to Deer Island, where most subsequently perished.
Local legend suggests that the town was to be named for a Lord Lyttleton, who was to provide the town with a town bell. When he learned of the misspelling of the town name, he refused to provide the bell.
The minutemen and militia of Littleton marched and fought at Concord and the Battle Road on April 19, 1775. The town, according to local lore, did have a contingent of Loyalists who remained in town after the revolution and thwarted attempts to rename King Street as Main, Washington, or Adams Streets. This has been the source of ribbing from neighboring towns calling Littleton a Tory town.
Despite the influx of Roman Catholic immigrants from Ireland, Canada, and Italy, Littleton remained a predominantly Yankee town with the bulk of the population belonging to the Congregational Church of Littleton, The First Baptist Church, and First Church Unitarian churches. The Roman Catholic parish of St Anne's was established in 1947 followed by The Church of Jesus Christ of Latter-day Saints in 1979. From 1961 through 1989, on Harwood Ave, there was a United Church of Christ which was vacated when it merged with the Congregational Church.
The arrival of Digital Equipment Corp. (now part of Hewlett-Packard) in the 1970s made the town part of the Boston-area high-tech corridor. It built a very large facility on King Street near the Common as well as offices on Porter Road and Foster Street. In 2007, IBM purchased the King Street facility from Hewlett-Packard and announced it would become its main Massachusetts location.
Due to the Yankee character of the town, it was notedly dry during Prohibition and the Rowse family, which then owned New England Apple Products (later Veryfine), were known for their integrity and honesty characterized by their refusal to do business with bootleggers in a state where Prohibition was overwhelmingly unpopular. Alcohol was first allowed to be sold in Littleton in 1960 in two locations, the Johnson's store at the Depot and Nashoba Package store at Donelan's shopping center. Only in the late 1980s with the building of DEC's King Street facility was a bar allowed to open in town (now Ken's American Cafe, followed by what is now the Chip Shot on Ayer Road). For years there were establishments that served alcohol just over the town line in Acton, Westford, Groton, Ayer, and Boxborough.
Many of the early settling families have remained in the town to present day: Blanchard, Bulkeley, Crane, Hartwell, Hathaway, Kimball, and Whitcomb. The neighborhoods around Mill Pond (also known as Lake Warren), Long Lake, Forge Village, and Spectacle pond include numerous summer cottages or "camps" that have been converted into year-round residences. Many of the Irish, Italian, Québécois, and Finnish families ended up moving to Littleton in the 1950s and 1960s after coming out from their neighborhoods in Arlington, East Boston, Cambridge, Lowell, and Somerville.
Due to its location between Fort Devens and Hanscom AFB, Littleton became a popular location for military retirees from the 1960s to the present day.
Residential development occurred in the postwar years in several spurts. In the late 1940s to 1950, cottages around Long Lake off Goldsmith, on the Littleton side of Forge Pond (called Lake Mattawanakee), along Spectacle Pond, and beside Mill Pond off Harwood Ave were either winterized or torn down and replaced by bungalows and Capes. At the same time, new construction went up along New Estate Road, Whitcomb Ave, and Tahattawan Road. From 1955 through 1965, Snow Village (off Great Road about a quarter mile before Power Road - formerly Snake Hill Road), Edsel Road (Kimball land behind the current Post Office running up the hill on the right of Goldmith Street), and lower Hartwell Ave (in the subdivision abutted by the cemetery, King St, and Hartwell Ave) were built with ranch houses and larger Capes. In the late 60s and early 1970s, stretches along Harvard Road, Taylor Street, Liberty Square, Foster Street, Mill Road, and Grist Mill Road saw some of the first split-levels and five-bedroom Colonials go up. In the late 1970s and early 1980s, the farms between Hartwell Ave and Great Road were developed along with upper Hartwell Ave. In this period, the livery stable at the corner of Coughlin Road and Newtown Road sold off more than half of its land to developers. In the late 80s and early 90s, the horse farms along Russell Street off Great Road closed and were developed as well as some of the horse farms off Harwood by the quarantine station. The turn of the century has seen further building of quite large Colonials along Great Road, on Fort Pond Hill, and along Beaver Brook Road.
There were 2,960 households out of which 37.8% had children under the age of 18 living with them, 64.6% were married couples living together, 7.7% had a female householder with no husband present, and 25.1% were non-families. 19.6% of all households were made up of individuals and 8.2% had someone living alone who was 65 years of age or older. The average household size was 2.72 and the average family size was 3.16.
In the town the population was spread out with 27.1% under the age of 18, 4.4% from 18 to 24, 33.0% from 25 to 44, 23.7% from 45 to 64, and 11.8% who were 65 years of age or older. The median age was 38 years. For every 100 females there were 92.2 males. For every 100 females age 18 and over, there were 92.9 males.
The median income for a household in the town was $71,384, and the median income for a family was $83,365. Males had a median income of $54,097 versus $43,966 for females. The per capita income for the town was $31,070. About 2.4% of families and 3.6% of the population were below the poverty line, including 1.9% of those under age 18 and 5.2% of those age 65 or over.
Freight travels daily through Littleton over the tracks of the historic Stony Brook Railroad. The line currently serves as a major corridor of Pan Am Railway's District 3 which connects New Hampshire and Maine with western Massachusetts, Vermont, and New York.