Middleton Place was established early in the life of the Carolina colony and served as a base of operations for a great Low Country planter family and was home to a dynamic African-American slave community. Begun in 1741 by Henry Middleton, President of the First Continental Congress, the 60-acre landscaped garden was both an intellectual and emotional focus for successive generations of Middletons.

Until 1865, the garden was nurtured and embellished by Henry's son, Arthur Middleton, a signer of the Declaration of Independence; Arthur Middleton's son, Henry Middleton, who was Governor of South Carolina and U.S. Minister to Russia; and Governor Henry Middleton's son, Williams Middleton, who signed the Ordinance of Secession. Despite long absences prompted by education abroad, military service, and public and diplomatic careers, Middleton family members have always returned to this Ashley River plantation.