John Drayton (c. 1715-1779) was born on the plantation now known as Magnolia Plantation and Its Gardens, located just north of Drayton Hall along the Ashley River. The Drayton family had come to South Carolina from England via Barbados in the late 17th century. As the third son of Thomas and Ann Drayton, John did not stand to inherit his family's plantation, and in 1738 he purchased the 350-acre plantation just to the south of them.

John married four times. His first wife Sarah Cattell was the daughter of a neighboring plantation owner; she and their two children died before 1740. In 1741 John Drayton married Charlotta Bull, daughter of South Carolina's Lt. Royal Governor William Bull; they had two sons, William Henry and Charles. Charlotta died in 1743. In 1752, John married Margaret Glen, the sister of James Glen, the Royal Governor; John and Margaret also had two sons, Glen and Thomas. Throughout much of the 1740s and 1750s, John managed Drayton Hall directly with no overseer. Margaret died 20 years later in 1772. In 1775, John married Rebecca Perry, the 17-year old daughter of a neighboring plantation owner. Rebecca and John had two daughters, Anna and Susannah, and a son, John.

In 1779 the British army arrived at Drayton Hall. In anticipation of their arrival, and the destruction they wrought, John and his family packed what they could and left. While crossing the west branch of the Cooper River at Strawberry Ferry, John suffered a seizure, died, and was buried in an unmarked grave. At his death, Rebecca inherited the property.