The site was purchased in 1941, totaling 17,232 acres (6,974 ha) of largely rural land. The towns of Hamburg, Howell, and Toonerville and around 700 citizens of the area were displaced beginning in 1940 and ending the following year. From 1941 to 1945, the Atlas Powder Company manufactured trinitrotoluene (TNT) and dinitrotoluene (DNT) at the site. Four TNT and two DNT production lines were situated on what was to be the Chemical Plant. These operations resulted in nitroaromatic contamination of soil, sediments, and some off-site springs. After World War II, over 15,000 acres (61 km2) were transferred to the State of Missouri, including the 6,987-acre (28.28 km2) August A. Busch Memorial Conservation Area. Additional land was transferred to the University of Missouri, St. Charles County, and the Francis Howell School District. Much of the land that was transferred to the University of Missouri has become the 8,398-acre (33.99 km2) Weldon Spring Conservation Area.
Following a considerable amount of environmental remediation of the facility by the U.S. Army and the Atlas Powder Company, 205 acres (83 ha) of the former ordnance works were transferred to the United States Atomic Energy Commission (AEC) in 1955 for construction of the Weldon Spring Uranium Feed Materials Plant, now referred to as the Weldon Spring Chemical Plant. Mallinckrodt, Inc. operated the plant from 1957 to 1966 under a contract with the AEC. An additional 14.88 acres (6.02 ha) were transferred to the AEC in 1964. The plant converted processed uranium ore concentrates to uranium tetrafluoride, uranium trioxide, intermediate compounds, and uranium metal. A small amount of thorium was also processed. Wastes generated during these operations were stored in four raffinate pits located on the plant property. Uranium processing operations resulted in radiological contamination of the area.
Uranium processing operations ceased in 1966, and on December 31, 1967, the AEC returned the facility to the Army for use as a defoliant production plant. The defoliant project was canceled before any process equipment was installed, and the Army transferred 50.65 acres (20.50 ha) of land encompassing the raffinate pits back to the AEC while retaining the Chemical Plant. The AEC, and subsequently the United States Department of Energy (DOE), managed the site, including the Army-owned Chemical Plant, under caretaker status from 1968 through 1985. In 1984, the Army repaired several of the buildings at the Chemical Plant, decontaminated some of the floors, walls, and ceilings, and isolated some equipment. In 1985, the Army transferred full custody of the Chemical Plant to the United States Department of Energy (DOE), at which time the DOE designated control and decontamination of the Chemical Plant, raffinate pits, and Quarry as a major project. The DOE legacy management web site has additional documentation on the status of the site.
The Weldon Spring Quarry was mined for limestone aggregate used in construction of the ordnance works. The Army also used the quarry for burning wastes from explosives manufacturing and disposal of TNT-contaminated rubble during operation of the ordnance works. These activities resulted in contamination of the soil and groundwater at the quarry.
In 1958, the Army transferred the Weldon Spring Quarry to the Atomic Energy Commission, who used it from 1959 to 1966 as a disposal area for uranium, thorium, and radium residues from the Chemical Plant (both drummed and uncontained) and for disposal of contaminated building rubble, process equipment, and soils from demolition of a uranium processing facility in St. Louis. Radiological contamination occurred in the same locations as the nitroaromatic contamination.