Natick was settled in 1651 by John Eliot, a Puritan missionary born in Widford, Hertfordshire, England, who received a commission and funds from England’s Long Parliament to settle the Massachusett Indians called Praying Indians on both sides of the Charles River, on land deeded from the settlement at Dedham. Natick was the first of Eliot’s network of praying towns and served as their center for a long time. While the towns were largely self-governing under Indian leaders, such as Waban and Cutshamekin, the praying Indians were subject to rules governing conformity to English Puritan culture (in practice Natick, like the other praying towns, combined both traditional and English culture and practices). Eliot and Praying Indian translators printed America’s first Algonquian language Bible. Eventually, the church in Natick was led for several decades by an indigenous pastor, Rev. Daniel Takawambait.

The colonial government placed such settlements in a ring of villages around Boston as a defensive strategy. Natick was the first and best documented settlement. The land was granted by the General Court as part of the Dedham Grant.

After a period of expansion and little focus on evangelism, Reverend John Robinson told the New Englanders to prioritize missionary work over growth, “the killing of those poor Indians….How happy a thing it had been if you had converted some before you had killed any.” Chastened in the wake of the Mystic Massacre of the Pequots, sincere efforts at evangelizing began. A school was set up, a government established, and the Indians were encouraged to convert to Christianity. In November 1675, during King Philip’s War, the Natick Indians were sent to Deer Island. Many died of disease and cold, and those who survived found their homes destroyed. The Indian village did not fully recover, and the land held in common by the Indian community was slowly sold to white settlers to cover debts. By 1785, most of the Natick Indians had drifted away. After King Philip’s War, Elliot’s and a few other missionaries’ opposition to the executions and enslavement of Indians were eventually silenced by death threats.

In 1775, both English and Praying Indian citizens of Natick participated in the Battles of Lexington and Bunker Hill, as well as serving in the Continental Army. The names of Natick’s Praying Indian soldiers are memorialized on a stone marker, along with all of Natick’s Revolutionary War veterans, on a stone marker on Pond Street, near downtown Natick.

The town was incorporated in 1781. Henry Wilson, a U.S. senator who became the 18th Vice President of the United States (1873–1875), lived most of his life in Natick as a shoemaker and schoolteacher known as the “Natick Cobbler” and is buried there. He is the namesake of one of Natick’s middle schools.

Though Natick was primarily a farming town, the invention of the sewing machine in 1858 led to the growth of several shoe factories. The business flourished and peaked by 1880, when Natick, with 23 operating factories, was third in the nation in the quantity of shoes produced. The shoes made in Natick were primarily heavy work shoes with only one or two companies making lighter dress shoes. Natick was famous for its brogan (shoes), a heavy ankle-high boot worn by soldiers in the American Civil War.

The wound core for a more resilient baseball was developed by John W. Walcott and combined with the figure-eight stitching devised by Colonel William A. Cutler. It was manufactured by the firm of H. Harwood & Sons in their factory, the world’s first plant for the manufacture of baseballs. In 1988 H. Harwood & Sons was converted into baseball factory condominiums.

In 1874, a fire in downtown Natick demolished 18 business blocks, two shoe factories, the Town Hall, Natick’s only fire engine house and the Congregational Church, as well as many private homes. Though no lives were lost, the loss of property was greater in proportion to the town’s wealth than the Great Chicago Fire of 1871. In 1875, Natick’s new Central Fire Station was completed on Summer Street and opened with grand ceremony on the same city block where the fire was first discovered. The Central Fire Station is now the home of The Center for Arts in Natick (TCAN), a private nonprofit performing arts center.

In 1891, a team from the town fire department won “The World’s Hook and Ladder Championship”, a competition between the fire departments of four area towns. The victory gave the town its nickname “Home of Champions”.

Miles 8 through 12 of the Boston Marathon run through Natick on Patriots’ Day every year along Route 135/Central St., and thousands of residents and visitors line the road to watch.

As of the census of 2010, there were 32,786 people, 13,080 households, and 8,528 families residing in the town. The population density was 2,132.9 people per square mile (823.7/km²). There were 13,368 housing units at an average density of 886.3 per square mile (342.3/km²). The racial makeup of the town was 85.4% White, 2% African American, 0.1% Native American, 7.2% Asian, 0.0% Pacific Islander, 0.5% from other races and 2% from two or more races. Hispanic or Latino of any race were 3% of the population.

There were 13,080 households, out of which 30.3% had children under the age of 18 living with them, 54.5% were married couples living together, 8.2% had a female householder with no husband present, and 34.8% were non-families. Of all households, 28.3% were made up of individuals, and 9.8% had someone living alone who was 65 years of age or older. The average household size was 2.42 and the average family size was 3.02.

In the town, the population was spread out, with 23.0% under the age of 18, 5.1% from 18 to 24, 34.3% from 25 to 44, 23.3% from 45 to 64, and 14.3% who were 65 years of age or older. The median age was 38 years. For every 100 females, there were 89.7 males. For every 100 females age 18 and over, there were 85.3 males.

According to a 2007 estimate, the median income for a household in the town was $61,855, and the median income for a family was $85,056. Males had a median income of $51,964 versus $41,060 for females. The per capita income for the town was $36,358. About 1.7% of families and 2.8% 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.

Natick is surrounded, on three sides, by five of the eleven most affluent towns in Massachusetts with Wayland to the north, Weston to the northeast, Wellesley to the east, Dover to the southeast, and Sherborn to the southwest.

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Natick has representative town meeting form of government (consisting of 180 members) with a Board of Selectmen and a Town Administrator. The members of the Board and the dates their terms end are (as of March 2019): { {Div col|colwidth=24em}}

The town is part of the Massachusetts Senate’s Norfolk, Bristol and Middlesex district.

Mismanagement of Middlesex County’s public hospital in the mid-1990s left the county on the brink of insolvency, and in 1997 the Massachusetts legislature stepped in by assuming all assets and obligations of the county. The government of Middlesex County was officially abolished on July 11, 1997. The sheriff and some other regional officials with specific duties are still elected locally to perform duties within the county region, but there is no county council or commissioner. Communities are now granted the right to form their own regional compacts for sharing services.

These are the remaining elected officers for Middlesex County:

Natick Center station, in the downtown area, is served by the MBTA Commuter Rail Framingham/Worcester Line.

Bus service is provided in Natick by the MetroWest Regional Transit Authority.