Middlesex County is a county located in the Commonwealth of Massachusetts, United States. As of the 2020 census, the population was 1,632,002, making it the most populous county in both Massachusetts and New England and the 20th most populous county in the United States. This makes the county the most populous county on the East Coast outside of New York or Florida. Middlesex County is one of two U.S. counties (along with Santa Clara County, California) to be amongst the top 25 counties with the highest household income and the 25 most populated counties. It is included in the Census Bureau's Boston–Cambridge–Newton, MA–NH Metropolitan Statistical Area. As part of the 2020 United States census, the Commonwealth's mean center of population for that year was geo-centered in Middlesex County, in the town of Natick (this is not to be confused with the geographic center of Massachusetts, which is in Rutland, Worcester County).

On July 11, 1997, Massachusetts abolished the executive government of Middlesex County primarily due to the county's insolvency. Middlesex County continues to exist as a geographic boundary and is used primarily as district jurisdictions within the court system and for other administrative purposes; for example, as an election district. The National Weather Service weather alerts (such as severe thunderstorm warning) continue to localize based on Massachusetts's counties.

The county was created by the Massachusetts General Court on May 10, 1643, when it was ordered that "the whole plantation within this jurisdiction be divided into four shires." Middlesex initially contained Charlestown, Cambridge, Watertown, Sudbury, Concord, Woburn, Medford, and Reading. In 1649 the first Middlesex County Registry of Deeds was created in Cambridge.

On April 19, 1775, Middlesex was the site of the first armed conflict of the American Revolutionary War.

In 1855, the Massachusetts State Legislature created a minor Registry of Deeds for the Northern District of Middlesex County in Lowell.

In the late 19th century and early 20th century, Boston annexed several of its adjacent cities and towns including Charlestown and Brighton from Middlesex County, resulting in an enlargement and accretion toward Suffolk County.

Beginning prior to the dissolution of the executive county government, the county comprised two regions with separate county seats for administrative purposes:

Since the start of the 21st century, much of the current and former county offices have physically decentralized from the Cambridge seat, with the sole exceptions being the Registry of Deeds and the Middlesex Probate and Family Court, which both retain locations in Cambridge and Lowell. Since the first quarter of 2008, the Superior Courthouse has been seated in the city of Woburn; the Sheriff's Office is now administratively seated in the city of Medford and the Cambridge-based County Jail has since been amalgamated with another county jail facility in Billerica. The Cambridge District Court (which has jurisdiction for Arlington, Belmont and Cambridge); along with the Middlesex County District Attorney's Office, although not a part of the Middlesex County government, was also relatedly forced to relocate to Medford at the time of the closure of the Superior Courthouse building in Cambridge.