Milford was first settled in 1662 and was officially incorporated in 1780. It was originally the eastern part of Mendon, called "Mill River".
Milford is renowned for its pink Milford granite, discovered in 1870. Some of this granite has been used for buildings in New York City, Washington, D.C., and Paris, along with a number of war memorials and other monuments, including the Battle Monument at West Point.
Today, it is recognized, in part, for its health care facility—the Milford Regional Medical Center. In January 2008, the Center opened a cancer treatment facility with the Dana–Farber Cancer Institute. The Center is affiliated with UMass Medical Center as a teaching hospital.
Milford is also the home of the "My One Wish" foundation, started in 1984.