The Middlesex Mill was the first mill erected in Lowell in 1813, and was located at the junction of the Concord River and Pawtucket Canal. In 1830 Samuel Lawrence, William W. Stone, and others were incorporated as the Middlesex Manufacturing Company (also known as Middlesex Woolen Company) and took control of the property. Samuel Lawrence was the treasurer from 1840–1851.

The company included three mills, and also dye-houses, and was unusual among the mills of Lowell for the fact that it manufactured cashmeres (known as cassimeres) and woolens, rather than the cotton cloth usually manufactured in Lowell. (In fact, it was the only woolen mill in Lowell in 1845). At that time, it was the largest factory for the weaving of woolen goods in the country, making broadcloth, doeskins, cassimeres, shawls, and indigo-dyed coating for uniforms.

In 1845, Rev. Henry A. Miles wrote in his account that the mill used the wool which was the produce of 400,000 sheep in Vermont, New York, New Hampshire, Ohio, Pennsylvania, Illinois, and Missouri. He wrote that there was one large mill in 1845 that was seven stories high, 158 feet long, and 46 feet wide, and that another of nearly the same size was about to be erected.

According to Miles: "This company has two mills, one of which is very large, and two dye-houses. It manufactures broadcloths and cassimeres. It runs seven thousand two hundred spindles, forty-five looms for broadcloth, one hundred and thirty-two for cassimeres. It employs five hundred and fifty females, and two hundred and fifty males. It makes twelve thousand yards of cassimere per week, and two thousand two hundred yards of broadcloth. It works up one million pounds of wool per year, and three million teasles. It consumes annually six hundred tons of coal, one thousand five hundred cords of wood, fifteen thousand gallons of oil for oiling wool, and six thousand gallons of sperm oil."

The company went into bankruptcy in 1858 and was reorganized the following year. The company ceased to manufacture between 1912 and 1918, and its buildings and power rights were subsequently sold to the Ipswich [Hosiery] Mills. Ipswich went into receivership in 1928, and the real estate reverted to the Middlesex stockholders who voted in 1946 to sell what remained. In 1956 all remaining buildings were demolished.