Waltham was first settled in 1634 as part of Watertown and was officially incorporated as a separate town in 1738. Waltham had no recognizable town center until the 1830s, when the nearby Boston Manufacturing Company gave the town the land that now serves as its central square.

In the early 19th century, Francis Cabot Lowell and his friends and colleagues established in Waltham the Boston Manufacturing Company – the first integrated textile mill in the United States, with the goal of eliminating the problems of co-ordination, quality control, and shipping inherent in the subcontracting based textile industry. The Waltham–Lowell system of production derives its name from the city and the founder of the mill.

The city is home to a number of large estates, including Gore Place, a mansion built in 1806 for former Massachusetts governor Christopher Gore, the Robert Treat Paine Estate, a residence designed by architect Henry Hobson Richardson and landscape architect Frederick Law Olmsted for philanthropist Robert Treat Paine, Jr. (1810–1905), and the Lyman Estate, a 400-acre (1.6 km²) estate built in 1793 by Boston merchant Theodore Lyman.

In 1857, the Waltham Model 1857 watch was produced by the American Watch Company in the city of Waltham, Massachusetts. In the late 19th and early 20th century, Waltham was home to the brass era automobile manufacturer Metz, where the first production motorcycle in the U.S. was built.

Another first in Waltham industrial history involves the method to mass-produce the magnetron tube, invented by Percy Spencer at Raytheon. During World War II, the magnetron tube technology was applied to radar. Later, magnetron tubes were used as components in microwave ovens.

Waltham was also the home of the Walter E. Fernald State School, the western hemisphere’s oldest publicly funded institution serving people with developmental disabilities. The storied and controversial history of the institution has long been covered by local and, at times, national media.^{[citation needed]}

The name of the city is pronounced with the primary stress on the first syllable and a full vowel in the second syllable, WAWL-tham, though the name of the Waltham watch was pronounced with a reduced schwa in the second syllable: . As most would pronounce in the British way, “Walthum”, when people came to work in the mills from Nova Scotia, the pronunciation evolved. The “local” version became a phonetic sounding to accommodate French speakers who could not pronounce in the British way.

Waltham is located at 42°22′50″N 71°14′6″W / 42.38056°N 71.23500°W / 42.38056; -71.23500 (42.380596, −71.235005), about 11 miles (18 km) north-west of downtown Boston, Massachusetts, and approximately 3 miles (4.8 km) northwest of Boston’s Brighton neighborhood. The heart of the city is Waltham Common, which is home to the City Hall and various memorial statues. The Common is on Main Street, which is home to several churches, the town library and Post Office.

The city stretches along the Charles River and contains several dams. The dams were used to power textile mills and other endeavors in the early years of the industrial activity.

According to the United States Census Bureau, the city has a total area of 13.6 square miles (35 km²), of which 12.7 square miles (33 km²) is land and 0.9 square miles (2.3 km²) (6.69%) is water.

Waltham has several neighborhoods or villages, including:

It is bordered to the west by Weston and Lincoln, to the south by Newton, to the east by Belmont and Watertown, and to the north by Lexington.

As of the census in 2000, there were 59,226 people, 23,207 households, and 12,462 families in the city. The population density was 4,663.4/mile² (1,800.6/km²). There were 23,880 housing units at an average density of 1,880.3 per square mile (726.0/km²). The racial makeup of the city was 82.98% White, 4.41% African American, 0.16% Native American, 7.29% Asian, 0.06% Pacific Islander, 3.20% from other races, and 1.89% from two or more races. Hispanic or Latino of any race were 8.49% of the population.

There were 23,207 households, of which 20.3% included those under the age of 18, 41.3% were married couples living together, 8.9% were headed by a single mother, and 46.3% were non-families. 34.2% of all households were made up of individuals, and 10.0% had someone living alone who was 65 or older. The average household size was 2.29 and the average family size was 3.01.

The age distribution is as follows: 15.5% under 18, 16.8% from 18 to 24, 34.4% from 25 to 44, 20.2% from 45 to 64, and 13.1% 65 or older. The median age was 34. For every 100 females, there were 97.2 males. For every 100 females 18 and over, there were 95.6 males.

The median income for a household was $54,010, and the median income for a family was $64,595. These figures increased to $60,434 and $79,877, respectively, according to an estimate in 2007. Males had a median income of $42,324, as opposed to $33,931 for females. The per capita income was $26,364. 7% of the population and 3.6% of families lived below the poverty line. 4.8% of those under 18 and 8.4% of those 65 and older lived below the poverty line.

As of 2010, 24% of the residents were born outside of the United States. Many originated from Guatemala and India.

Waltham is governed by a mayor and a city council. The current mayor is Jeanette A. McCarthy. There are 15 members of the city council, each elected to two-year terms in non-partisan elections. The current president of the city council is Paul J. Brasco.

The city is in Massachusetts’s 5th congressional district and is currently represented in the United States House of Representatives by Katherine Clark. Waltham is also represented in the Massachusetts House of Representatives by State Representative John J. Lawn and State Representative Thomas M. Stanley, and in the Massachusetts Senate by Senator Michael Barrett.