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 sheires". Middlesex initially contained Charlestown, Cambridge, Watertown, Sudbury, Concord, Woburn, Medford, and Reading.
As of the census of 2000, there were 1,465,396 people, 561,220 households, and 360,864 families residing in the county. The population density was 1,780/sq mi (687/km²). There were 576,681 housing units at an average density of 700 per square mile (270/km²). The racial makeup of the county was 85.88% White, 3.36% Black or African American, 0.15% Native American, 6.26% Asian, 0.04% Pacific Islander, 2.07% from other races, and 2.24% from two or more races. 4.55% of the population were Hispanic or Latino of any race. 20.0% were of Irish, 15.7% Italian and 8.0% English ancestry according to Census 2000. 79.6% spoke English, 4.3% Spanish, 2.7% Portuguese, 1.6% Italian, 1.6% Chinese or Mandarin and 1.5% French as their first language. Middlesex County has the largest Irish-American population of any U.S. county with a plurality of Irish ancestry. [9]
There were 561,220 households out of which 30.20% had children under the age of 18 living with them, 51.30% were married couples living together, 9.90% had a female householder with no husband present, and 35.70% were non-families. 27.10% of all households were made up of individuals and 9.50% had someone living alone who was 65 years of age or older. The average household size was 2.52 and the average family size was 3.11.
In the county the population was spread out with 22.50% under the age of 18, 9.00% from 18 to 24, 33.40% from 25 to 44, 22.40% from 45 to 64, and 12.80% who were 65 years of age or older. The median age was 36 years. For every 100 females there were 93.70 males. For every 100 females age 18 and over, there were 90.70 males.
The median income for a household in the county was $60,821, and the median income for a family was $74,194 (these figures had risen to $74,010 and $91,461 respectively as of a 2007 estimate). Males had a median income of $49,460 versus $36,288 for females. The per capita income for the county was $31,199. About 4.30% of families and 6.50% of the population were below the poverty line, including 7.20% of those under age 18 and 7.10% of those age 65 or over.