Wrentham was first settled by the English in 1661 and officially incorporated in 1673. It was burned down during King Philip's War 1675-1676. For a short time, it was the residence of the educational reformer Horace Mann. It is also known as one of the residences of Helen Keller.

According to the United States Census Bureau, the town has a total area of 22.9 square miles (59 km²), of which 22.2 square miles (57 km²) is land and 0.7 square miles (1.8 km²) (3.14%) is water. Wrentham is bordered by Norfolk on the north, Foxboro on the east, Plainville and Cumberland, Rhode Island on the south, Bellingham on the southwest, and Franklin on the west. It has two large lakes towards the center of town, Lake Pearl and Lake Archer, as well as Mirror Lake on the Wrentham/Norfolk border and numerous smaller lakes. Sheldonville, or West Wrentham, is a rural section of Wrentham located on the western leg of town. Sheldonville still maintains a unique identity as the old farming section of Wrentham, has active commercial orchards, and has its own ZIP code (02070). Wrentham drains into four watersheds. They are the Charles River to the North, the Taunton River to the East, the Blackstone River to the West, and the Ten Mile River to the South.

Wrentham is the only town of that name in the United States. It is named after the village of Wrentham in Beccles, Suffolk, England. The only other Wrentham is Wrentham, Alberta. Wrentham, Massachusetts, is by far the most populous of the three.

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