Tewksbury was first settled in 1637 and was officially incorporated on December 17, 1734, from Billerica. There is no evidence that the town was named after Tewkesbury, England. Still, Tewksbury, Massachusetts and Tewkesbury, England kept connected through a local committee called the twinning committee. One of the oldest sections of town is the area around the Shawsheen River. This is where the Shawshin tribe settled, allowing them access to a great food source through fishing in the river. Tewksbury was also known for a historic visit by President Andrew Jackson, stopping off at local watering hole, Brown’s Tavern.

On July 24, 1857, a powerful tornado swept through Tewksbury. The tempest began at Round Pond as a small water spout, and traveled west and then southeast to the Shawsheen River. It dissipated at North Wilmington. Several corn fields and orchards were severely damaged, with one residence having its roof blown off. The tornado was powerful enough to flatten barns and sheds, pull up large trees by their roots, and sweep away and kill a team of oxen. Due to the sparse population, and homes located above the valley floor, no one was killed, and only a few people were injured.

According to the United States Census Bureau, the town has a total area of 21.1 square miles (55 km²), of which 20.7 square miles (54 km²) is land and 0.3 square miles (0.78 km²), or 1.61%, is water.

The Merrimack River forms part of the northern boundary of Tewksbury, and the Shawsheen River runs through the southern end of town as well.

Tewksbury is in the Greater Lowell metropolitan area. The town is located about 19 miles (31 km) north-northwest of Boston along I-93 and I-495 (Boston’s outer beltway). Tewksbury is bordered by the city of Lowell to the northwest, Dracut to the north (unreachable across the Merrimack), Andover to the northeast, Wilmington to the southeast, and Billerica to the southwest. Tewksbury also meets the town of Chelmsford at a point in the middle^{[citation needed]} of the Concord River along with Lowell and Billerica.

As of the census of 2000, there were 28,851 people, 9,964 households, and 7,692 families residing in the town. The population density was 1,392.3 people per square mile (537.6/km²). There were 10,158 housing units at an average density of 490.2 per square mile (189.3/km²). The racial makeup of the town was 96.44% White, 0.67% African American, 0.12% Native American, 1.59% Asian, 0.01% Pacific Islander, 0.41% from other races, and 0.75% from two or more races. Hispanic or Latino of any race were 1.22% of the population.

There were 9,964 households, out of which 35.9% had children under the age of 18 living with them, 65.1% were married couples living together, 9.1% had a female householder with no husband present, and 22.8% were non-families. Of all households 18.9% were made up of individuals, and 7.2% had someone living alone who was 65 years of age or older. The average household size was 2.81 and the average family size was 3.24.

The town’s population was spread out, with 25.0% under the age of 18, 6.2% from 18 to 24, 32.8% from 25 to 44, 24.6% from 45 to 64, and 11.5% who were 65 years of age or older. The median age was 38 years. For every 100 females, there were 96.1 males. For every 100 females age 18 and over, there were 93.7 males.

The median income for a household in the town was $68,800, and the median income for a family was $76,443. Males had a median income of $50,296 versus $33,918 for females. The per capita income for the town was $27,031. About 1.9% of families and 3.8% of the population were below the poverty line, including 2.4% of those under age 18 and 5.3% of those age 65 or over.

Tewksbury, like most towns in Massachusetts, operates under a New England town form of government. Day-to-day management is led by a Town Manager, who reports to the town’s five member Board of Selectmen. Every spring the town holds an Open Town Meeting where the budget is submitted for approval by the town’s citizens.

Tewksbury is located in the 6th Congressional District and thus represented in the House of Representatives by Seth Moulton of Salem. In the Senate by Senators Ed Markey of Malden and Elizabeth Warren of Cambridge.

Tewksbury is one of the more Republican-leaning towns in the Commonwealth. It was one of the few communities who supported John McCain over Barack Obama in the 2008 Presidential Election. In the special election to replace the late Ted Kennedy, Tewksbury supported Scott Brown over Martha Coakley by a 2-to-1 margin.

The former Tew-Mac Airport was located in the town before it was closed in 1997 and replaced with condos and a country club.

The LRTA 12 bus connects Tewksbury to Lowell and Wilmington on the MBTA Commuter Rail Lowell Line. In July 2017, Massachusetts Governor Charlie Baker and other Baker administration transportation officials visited a construction project in the city to highlight $2.8 billion spent during Baker’s administration on highway construction projects and improvements to bridges, intersections, and sidewalks.