During the American Revolutionary War the city became the British military and political base of operations in North America, following the departure of General George Washington and the Continental Army shortly after Battle of Long Island and subsequent local defeats. Under British occupation clergy were required to be Loyalists, while the parishioners included some members of the revolutionary New York Provincial Congress, as well as the First and Second Continental Congresses.

The church was destroyed in the Great New York City Fire of 1776, which started in the Fighting Cocks Tavern, destroying between 400 and 500 buildings and houses, and leaving thousands of New Yorkers homeless. Six days later, most of the city's volunteer firemen followed General Washington north. Rev. Charles Inglis served throughout the war and then to Nova Scotia on evacuation with the whole congregation of Trinity Church.