Leicester was first settled in 1713 and was officially incorporated in 1714.
Although no significant battles of the American Revolution were fought in the area, Leicester citizens played a large role in the conflict's start. At a Committee of Safety meeting in 1774, Leicester's Colonel William Henshaw declared that "we must have companies of men ready to march upon a minute's notice"—coining the term "minutemen", a nickname for the militia members who fought in the revolution's first battles. Henshaw would later become an adjutant general to Artemas Ward, who was second in command to George Washington in the Continental Army.
Leicester's own standing militia fought along with other minutemen at the first conflict between Massachusetts residents and British troops, the Battles of Lexington and Concord on April 19, 1775. A few months later on June 17, 1775, a freed slave and Leicester resident named Peter Salem fought at the Battle of Bunker Hill, where he killed British Major John Pitcairn. Both men are memorialized in Leicester street names (Peter Salem Road, Pitcairn Avenue).
Leicester also held a leading role in Massachusetts' second great revolution, the coming of industrialization. As early as the 1780s, Leicester's mills churned out one-third of American hand cards, which were tools for straightening fibers before spinning thread and weaving cloth. By the 1890s when Leicester industry began to fade, the town was producing one-third of all hand and machine cards in North America.
Ruth Henshaw Bascom (1772–1848), the wife of Reverend Ezekial Lysander Bascom and daughter of Colonel William Henshaw and Phebe Swan, became America's premier portrait folk artist and pastelist, producing over one thousand portraits from 1789 to 1846. (Henshaw Street was named after her.)
Eli Whitney, the man who invented the cotton gin and devised the idea of interchangeable parts, went to school at Leicester Academy, which eventually became Leicester High School. Ebenezer Adams, who would later be the first mathematics and natural philosophy professor at the Phillips Exeter Academy in New Hampshire, was the academic preceptor in Leicester in 1792. Leicester's Pliny Earle helped Samuel Slater build the first American mill in Pawtucket, Rhode Island, by building the first carding machine. This began the American Industrial Revolution. Leicester today is one of the most northernmost communities within the Blackstone River Valley, National Heritage Corridor. Its early role with carding machines, and the role that Pliny Earle played with the first water powered mill at Pawtucket, complete the case for inclusion on Leicester in this Federal NPS historic designation.
Other social leaders who came from Leicester include Charles Adams, military officer and foreign minister, born in town; Emory Washburn, governor of Massachusetts from 1854–1855; and Samuel May, a pastor and active abolitionist in the 1860s, whose house was a stop on the Underground Railroad. He also served as secretary of the Massachusetts Anti-Slave Society. His house has become a part of the Becker College campus.
In 2005, the Worcester Telegram & Gazette named Leicester one of Central Massachusetts' top ten sports towns.