The territory that Medfield now occupies was, at the time of colonization, Neponset land. After the English took the Native Americans’ land by force and spread a variety of diseases to the people, it was apparently sold by the Neponset leader Chickatabot to William Pynchon in the late 1620s. In 1633, however, Chickatabot died in a smallpox epidemic that decimated nearby Neponset, Narragansett and Pequot communities. Because Chickatabot and Pynchon’s deal left no written deed, the Massachusetts General Court ordered “those Indians who were present when Chickatabot sold lands to Mr. Pynchon, or who know where they were, to set out the bounds thereof”. Fifty years later, Chickatabot’s grandson Josias Wampatuck brought a land claim against Medfield and the other towns created within the borders of the Chickatabot purchase, for which he received payment. Of those lands, Dedham was the first town formed.

Dedham was incorporated in 1636, and Medfield (New Dedham) was first settled in 1649, principally by people who relocated from the former town. The first 13 house lots were laid out on June 19, 1650. In May 1651, the town was incorporated by an act of the General Court as the 43rd town in Massachusetts.

The Rev. Ralph Wheelock is credited with the founding of Medfield. He was the first schoolmaster of the town’s school established in 1655, and now has an elementary school named after him.

Half the town (32 houses, two mills, many barns and other buildings) was destroyed by Native Americans during King Philip’s War in 1675. One house, known as the Peak House, was burnt in the war but was rebuilt shortly thereafter near downtown Medfield.

The town’s boundaries originally extended into present-day Medway and Millis. In 1713 the town was divided, with the section west of the Charles River becoming the new town of Medway.

According to the United States Census Bureau, the town has a total area of 14.6 square miles (37.8 km²), of which 14.5 square miles (37.6 km²) is land and 0.1 square mile (0.2 km²) (0.62%) is water. The Charles River borders almost one-third of Medfield. Medfield is surrounded by the towns Dover, Norfolk, Walpole, Millis, and Sherborn. The Charles River marks the Millis border.

Hispanic or Latino of any race were 0.90% of the population.