The Quincy family was one of the leading families in Massachusetts from the 17th to the 19th century. Descendants included several prominent Edmund Quincys and Josiah Quincys, and John Quincy Adams, through his mother, First Lady Abigail Adams. The Quincys settled in what is now Quincy in the 1630s, which at the time was part of Braintree, MA.

Edmund Quincy II built the homestead in 1686. It became a gathering place for many American Revolutionary War patriots, including John Adams, Colonel John Quincy, and John Hancock. It was also the childhood home of Dorothy Quincy Hancock Scott, wife of John Hancock and the first First Lady of Massachusetts. The original property was around 200 acres, and included the Dorothy Quincy Home, the Josiah Quincy House and the Josiah Quincy Mansion. 

It represents over 320 years of American architectural evolution, combining Colonial, Georgian, and Victorian design elements. It is a rare Massachusetts example where elements of a 17th-century building remain clearly visible despite the addition of later styles.

The Homestead is owned by the Commonwealth of Massachusetts and operated by The National Society of the Colonial Dames of America through a public-private partnership. In 1904, when the property was threatened by urban development, a citizen drive led by the Massachusetts Colonial Dames and Charles Francis Adams, Jr., the grandson of President John Quincy Adams, successfully raised funds to purchase the estate. The Colonial Dames created a distinctive house museum and negotiated a sale-leaseback agreement with the Commonwealth. This agreement placed the Commonwealth in charge of capital improvements and exterior preservation, while the Dames maintained the interior, decorated it with period furniture and decorative arts, and interpreted its history for the public. This partnership has continued for over a century. 

In 2005, the Quincy Homestead was designated a National Historic Landmark. The same year, the Dorothy Quincy Homestead underwent a comprehensive exterior renovation to restore the historic building to its former grandeur. This project included painting the structure, re-glazing the windows, and other major improvements.