John Williams, an early South Carolina planter, probably began building Middleton Place in the late 1730s. His son-in-law Henry Middleton (1717–1784), who later served as President of the First Continental Congress, completed the house's main section and its north and south flankers, and began work on the elaborate gardens. Middleton's son, Founding Father Arthur Middleton (1742–1787), a signer of Declaration of Independence, was born at Middleton Place, and lived at the plantation in the last years of his life. Arthur Middleton's son and grandson, Henry Middleton (17701846) and Williams Middleton (1809–1883), oversaw Middleton Place's transition from a country residence to a more active rice plantation. In 1865, toward the end of the American Civil War, Union soldiers burned most of the house, leaving only the south wing and gutted walls of the north wing and main house. In 1886, the eponymous 1886 Charleston earthquake toppled the walls of the main house and north wing.
