English colonists first settled the area now incorporated as the town of Carlisle in 1651 on parcels of land of the neighboring towns of Acton, Billerica, Chelmsford and Concord. Carlisle became a district of Concord in 1780 and was incorporated as a town by an act of the legislature in 1805.

Carlisle is located about 8 miles (13 km) south-southwest of Lowell and 19 miles (31 km) northwest of Boston. It borders the towns of Concord, Acton, Westford, Chelmsford, Billerica, and Bedford.

According to the United States Census Bureau, the town has a total area of 15.5 square miles (40 km²), of which 15.4 square miles (40 km²) is land and 0.2 square miles (0.52 km²) (1.09%) is water.

Conservation land makes up about a quarter of the town’s area. Besides town-owned land overseen by the town’s conservation committee, Carlisle is home to Great Brook Farm State Park and a portion of the Great Meadows National Wildlife Refuge neighboring the Concord River.

As of the census of 2000, there were 4,717 people, 1,618 households, and 1,372 families residing in the town. The population density was 307.1 people per square mile (118.6/km²). There were 1,655 housing units at an average density of 107.7 per square mile (41.6/km²). The racial makeup of the town was 93.47% White, 0.17% African American, 0.06% Native American, 4.83% Asian, 0.04% Pacific Islander, 0.13% from other races, and 1.29% from two or more races. Hispanic or Latino of any race were 1.19% of the population.

There were 1,618 households, out of which 46.4% had children under the age of 18 living with them, 78.6% were married couples living together, 4.7% had a female householder with no husband present, and 15.2% were non-families. 11.4% of all households were made up of individuals, and 4.9% had someone living alone who was 65 years of age or older. The average household size was 2.92 and the average family size was 3.18.

In the town, the population was spread out, with 30.6% under the age of 18, 3.4% from 18 to 24, 23.3% from 25 to 44, 34.3% from 45 to 64, and 8.4% who were 65 years of age or older. The median age was 42 years. For every 100 females, there were 98.3 males. For every 100 females age 18 and over, there were 96.4 males.

The median income for a household in the town $176,228 (Average household income is $244,544). The per capita income for the town was $87,470.

Carlisle maintains a 2-acre (8,100 m²) zoning law on new development.