[2][3] Will's Hill in modern-day Middleton was home to a winter village founded by an Algonquin Sachem.

[5] The name Middleton is derived from its location midway between the important early settlements of Salem and Andover.

It was first settled by Bray Wilkins, who came from Salem with a large family, having purchased 600 acres from Governor Bellingham.

The town grew as a farming community, mostly due to its location on the Ipswich River, with homesteads of hundreds of acres.

However, during the 18th century, Middleton also contained a vital ironworks industry, located in the area of what is now Mill and Liberty Streets.

Notably, the Essex Railroad had termini in Salem and North Andover, running through Middleton from the mid-1840s through the mid-20th century, when passenger and freight demands dropped off.

[8] In the late 18th and to the mid-19th centuries Middleton was a vacation town to those who lived in areas such as Lawrence and Lowell.

It is home to one of the oldest trees in Massachusetts, being approximately 400 years old, and which is located at 39 Peabody Street.

These three towns share Masconomet Regional High School (named after Chief Masconomet, sagamore of the Agawam tribe, which lived in Essex County at the time of English colonization) which serves grades 9–12, while its middle school serves grades 7 and 8.

Middleton lies along the border of Essex County, and is bounded by North Reading in Middlesex County to the west, and North Andover to the northwest, Boxford to the northeast, Topsfield to the east, Danvers to the southeast, Peabody to the south, and shares a 0.3 mile border with Lynnfield to the southwest.