Settled by European colonists in 1654 as a part of Lancaster, Clinton was incorporated in 1850. It was named after the DeWitt Clinton Hotel in New York by its founders, carpet loom inventor Erastus Brigham Bigelow and his brother Horatio, owners of the Bigelow Carpet Company. Erastus and Horatio provided an economic and civic base for the community, endowing local institutions including the Bigelow Free Public Library and the town common, which was named Central Park.

Located on the Nashua River, which provided the power for its 19th century mills, Clinton became home to Irish, German, Scottish and English immigrants. Construction on the Wachusett Dam began in 1897, culminating in the filling of the Wachusett Reservoir in 1908 which flooded a substantial portion of Clinton and neighboring towns, whose residents had to be relocated.
Clinton is home to the Museum of Russian Icons and lays claim to having the oldest continuously used baseball field in the world.