Mendon is a town in Worcester County, Massachusetts, United States. The population was 5,839 at the 2010 census. Mendon is very historic and is now part of the Blackstone River Valley National Heritage Corridor, the oldest industrialized region in the United States. Mendon celebrates its 350th Anniversary in 2017.

The Nipmuc people once inhabited Mendon, and Nipmuc Pond is named for them. Nipmuc Regional High School was named after this lake. Nipmuc means "small pond place" or "people of the fresh waters". The Nipmuc name does not refer to a specific village or tribe, but to natives that inhabited almost all of central Massachusetts. Over 500 Nipmuc live today in Massachusetts, and there are two nearby reservations at Grafton and Webster. The Nipmuc had a written language, tools, a graphite mine at Sturbridge, and well-developed agriculture, including maize (a variant of corn), beans and squash.

During King Philip's War in 1675, Praying Indians (natives who converted to Christianity) were settled into Praying Indian Villages. Wacentug and Rice City held two of these villages in Mendon, in a section that later became Uxbridge. These were two of the 14 Praying Indian villages established by Reverend John Eliot, from Natick and Roxbury, who translated the Bible into the Nipmuc language.

Pioneers from Braintree petitioned to receive a land grant for 8 miles (13 km) square of land, 15 miles (24 km) west of Medfield. In September 1662, after the deed was signed with a Native American chief, "Great John", the pioneers entered this part of what is now southern Worcester County. Earlier, unofficial, settlement occurred here in the 1640s, by pioneers from Roxbury. This was the beginning of Mendon.

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