E.I. du Pont de Nemours & Company was established in 1802 by Pierre Samuel du Pont de Nemours (1739-1817) and his son Éleuthère Irénée du Pont (1771-1834). Built along the banks of the Brandywine River north of Wilmington, Delaware, the mill refined its first saltpeter in 1803 and its first gunpowder the same year. Throughout the nineteenth century, the company continued to produce gunpowder before expanding into dynamite and smokeless powder production. In 1902, cousins T. Coleman, Pierre S., and Alfred I du Pont purchased the company and began to transform it from a primarily explosives-based operation to one focused on science and chemicals. Accordingly, the company began buying up smaller powder and chemical companies before anti-trust legislation forced the company to divest much of its interests. Despite the company’s intentions of closing the powder yard at the Brandywine Works in the early 1910s, the site remained in operation by request of the Federal Government until the end of World War I. The Brandywine Works closed in 1921.

Concurrent with the construction of the gunpowder yards in 1802 was the completion of Eleutherian Mills, the first du Pont family home built in America. Built by Éleuthère Irénée du Pont, the home sat on a hill and overlooked Brandywine Creek and the DuPont gunpowder yards. Members of the du Pont family constructed large houses throughout the Brandywine Valley, many of which were located within a three-mile radius, including Winterthur, Rencourt, Nemours, and Pelleport. Following the closure of the powder yards in 1921, the Brandywine Works and much of the surrounding property was divided among du Pont family members for estates. In 1952, members of the du Pont family donated much of the land on which the former powder yards stood, and the DuPont Company created an endowment for the Eleutherian Mills-Hagley Foundation for the purpose of preserving the site and establishing a museum. The site opened as a museum in 1957 and was designated a National historic Landmark in 1966.