Upton is a residential community with a proud history of farming and straw hat manufacturing. Early grist and sawmills could be found along the West River and streams and the Upton State Forest boasts three of the original Civilian Conservation Camp buildings from the 1930s. Upton provided soldiers for the Revolutionary War, had sympathizers with the Shays Rebellion and marched for the North in the Civil War. Dolly Keane provided secret housing for the Underground Railroad. There is a cave whose origin is uncertain - perhaps from the ancient Celtic tradition or only hundreds of years old made during colonial times. It was originally the home of the Nipmuc, who inhabited most of central Massachusetts. The town was first settled in 1728 and was officially incorporated in 1735.

Upton was home to a number of members of the Taft family, including an American Revolutionary War soldier named Samuel Taft, who was born there. Samuel Taft had 22 children and hosted President George Washington on his inaugural tour of New England in 1789. 

Between 1730 and 1850, Upton had many small shoe shops, called ten–footers. These operations were gradually merged into large assembly-line manufacturing companies. By 1837, Upton produced 21.7% of the boots made in Worcester County. 

William Knowlton founded what was to become the world’s largest women's hat factory: Knowlton Hat Factory was built in 1872 and added to the National Historic Register in 1982.