Middletown is a city located in Middlesex County, Connecticut, United States, Located along the Connecticut River, in the central part of the state, it is 16 miles (26 kilometers) south of Hartford. In 1650, it was incorporated by English settlers as a town under its original Native American name, Mattabeseck, after the local indigenous people, also known as the Mattabesett. They were among the many tribes along the Atlantic coast who spoke Algonquian languages. The colonists renamed the settlement in 1653.

When Hartford County was organized on May 10, 1666, Middletown was included within its boundaries. In 1784, the central settlement was incorporated as a city distinct from the town. Both were included within newly formed Middlesex County in May 1785. In 1923, the City of Middletown was consolidated with the Town, making the city limits extensive.

Originally developed as a sailing port and then an industrial center on the Connecticut River, it is now largely residential. Its downtown, based on Main Street, serves as a popular retail, dining, and bar district near Wesleyan University. Middletown was the county seat of Middlesex County from its creation in 1785 until the elimination of county government in 1960. As of the 2020 census, the city had a total population of 47,717. Making it the largest city outside of Fairfield County, Hartford County, and New Haven County. Middletown, Connecticut is considered the southernmost city in the Hartford-Springfield Knowledge Corridor Metropolitan Region, which features a combined metro population of 1.9 million. Middletown is largely a politically progressive city, and is home to one of the largest pride events in all of Connecticut.

The land on the western bank of the Connecticut River where Middletown now lies was home to the Mattabesett Native Americans (also spelled Mattabesec, Mattabeseck, and Mattabesek); the area they inhabited—now Middletown and the surrounding area—was named after them. At the time the first European settlers arrived in the region, who were primarily English, the Mattabesett were a part of the group of Algongquian-speaking tribes in the Connecticut Valley, that were under a single chief named Sowheag.

Plans for the colonial settlement were drawn up by the General Court in 1646; the first migrants came from nearby Connecticut colonies in 1650. On September 11, 1651, the General Court of Connecticut established the town of “Mattabesett”. A couple of years later in November 1653, the settlement was renamed as Middletown. This name was chosen because the site was approximately halfway between Windsor and Saybrook on the Great River. Life was not easy for these early colonial Puritans; clearing the land and building houses, and tending farms in the rocky soil of New England was a labor-intensive ordeal. They had a strict society; offenses legally punishable by death in the Connecticut colonies included “witchcraft, blasphemy, cursing or smiting of parents, and incorrigible stubbornness of children.”

The Pequot Mohegan, at that time traditional allies of the English colonists and enemies of the Mattabesett and other local tribes, arrived in the Middletown area in the latter half of the 17th century; conflict between them and local Native American tribes ensued. The Mattabesett and other tribes referred to the Mohegan as “destroyers of men.” Sowheag hoped that the colonists would intervene. They did not. Smallpox epidemics caused high mortality among the Mattabesett, reducing their ability to resist and disrupting their cohesion as a tribe. Records show that, over time, Sowheag was forced to sell off most of the Mattabesett property to the local colonists; by 1676 the Puritans owned all but 300 acres (1.2 km) of the former Mattabesett territory. Native Americans suffered similar fates of illness and dispossession at other colonial sites in 17th-century New England.