After the 1774 incident known as the Powder Alarm, an angry mob surrounded the Brattle mansion and forced the family to flee to Boston.

At age 70, Brattle left Boston for Halifax, Nova Scotia on Evacuation Day, March 17, 1776, and died a few months later on October 26, 1776.

[3][4] According to Edward Abbott, writing in 1859,[5] General Brattle conveyed all his real estate in Cambridge, December 13, 1774, to his only surviving son, Major Thomas Brattle... By the persevering efforts of Mrs. Katherine Wendell, the only surviving daughter of General Brattle, the estate was preserved from confiscation, and was recovered by Major Brattle after his return from Europe,—having been proscribed in 1778, and having subsequently exhibited satisfactory evidence of his friendship to his country and its political independence.Nevertheless, the home was used temporarily as a headquarters by Thomas Mifflin and hosted a number of important figures from the early Revolutionary War period, including John Adams, who visited here before his trip to Philadelphia to sign the Declaration of Independence.

[6] For a time, the William Brattle House was home to American journalist Margaret Fuller.

While living here on Christmas Day 1834, she ran out of a church service and had the inspirational thought "that there was no self; that selfishness was folly" and that she must teach herself to "act in cooperation with the constraints of life".