In June 1638, John Winthrop the Younger, son of the founder of the Massachusetts Bay Colony, bought most of present-day Essex County from Masconomet, chief of the Agawam Indians, for the sum of twenty English pounds. A memorial stone on Sagamore Hill in southeastern Hamilton marks where Mosconomet was buried with his gun and tomahawk around 1658.

Hamilton was first settled in 1638 and was originally a section of Ipswich known as "The Hamlet". The first recorded land grant in the Hamlet was Matthew Whipple's farm, dated 1638. Three years later the new stagecoach road from Boston to Newburyport (Bay Road) was laid out through the Whipple land. Other early settlers of the Hamlet, including the Appletons, Winthrops, Lamsons, and Dodges, were attracted by countryside similar to the English farms and estates they had left behind.

The town was incorporated on June 21, 1793, and named for Alexander Hamilton, whose portrait became the town seal in 1903. With the arrival of the Boston and Maine Railroad in 1839, the population center moved gradually southward toward the depot.

The farm village proved to be an attractive location for Boston groups seeking land for recreation and renewal. A Methodist ministers' association first held a camp meeting at Asbury Grove in 1859. In the 1880s, the Myopia Hunt Club, which had been named in jest for its nearsighted founders, moved from Winchester, Massachusetts, to the Gibney Farm in Hamilton. Beginning as a lawn tennis and baseball club, it turned to polo, the hunt, and golf as members built large summer estates in the area. Myopia donated the site for the General George S. Patton Memorial Park to the town of Hamilton. The park continues to be a recreation center for the town.

In 1921 the Mandell family built the Community House in memory of the eight men in Hamilton and Wenham who died in military service during World War I, including their son, Sam. They commissioned Guy Lowell, a respected architect of Boston and New York, to design the building, and gave the Community House in trust for the use of the residents of both towns. Although in its early days the Community House offered activities such as bowling and a men's smoking room, it now features a wide range of classes and activities for all ages.

• Asbury Grove

• Austin Brown House

• Brown House (Hamilton, Massachusetts)

• Emeline Patch House

• Hamilton Historic District

• Myopia Hunt Club, site of the U.S. Open in 1898, 1901, 1905, and 1908

• Woodberry-Quarrels House

Hamilton is esteemed for the regional school district it shares with neighboring Wenham, and Hamilton is where the majority of the schools in the Hamilton-Wenham Regional School District are located. Only Buker Elementary School is located outside the town, in Wenham.

At Hamilton-Wenham Regional High School, students' average SAT scores are above the state average (According to numbers released by the state Dept of Education, Hamilton-Wenham Regional High School ranked 27th in the state based on combined total SAT scores for the 2006/2007 school year), and the school regularly sends top students to Ivy League schools. Boston Magazine's 2010 issue showcasing a list of the best public high schools ranked Hamilton-Wenham Regional High School 12th, placing Hamilton-Wenham's public high school in the top 10 percent of the state overall. Hamilton-Wenham also had one of the highest graduation rates, at 96.8 percent. By 2011, Hamilton-Wenham Regional High School had moved up to number nine in Boston Magazine's "Best Schools" list. More recently, Hamilton-Wenham Regional High School ranked 107th (out of 14,000) on Newsweek's 2014 list of "America's Top High Schools" and Hamilton-Wenham Regional High School was ranked the 13th-best public high school in Massachusetts in the 2016 U.S. World & News Report rankings (the same report ranked Hamilton-Wenham 344th nationally.)

According to a September 29, 2010, article in the Hamilton-Wenham Chronicle: "Of the 885 schools in Massachusetts, the Bessie Buker Elementary School ranked second in science on this year's MCAS. The fifth-grade class at the school had 93 percent of its students score advanced and proficient. In addition, all ninth-grade students passed the biology test, with 92 percent scoring advanced and proficient, ranking 20th state-wide. Cutler School scored 21st state-wide with 90 percent of third-graders scoring advanced and proficient in English language arts.

The Pingree School, a private secondary school, is located on the historic Pingree Family Estate in Hamilton.

Hamilton is also home to Gordon-Conwell Theological Seminary, an interdenominational evangelical theological seminary.