Originally opened as a storage site for ammunition, as part of a general military expansion in the face of war in Europe and Asia, the Anniston Ordnance Depot was established in 1941 on 10,640 acres, conveniently close to Fort McClellan, then a major Army base. Soon, warehouses, administration buildings, and 500 ammunition igloo housing storage structures were built. Once the U.S entered World War II and Anniston Depot's services came into heavy demand, the army had to acquire more land to expand its facilities.

In 1952, and the depot began a new mission as what would become "the Tank Rebuild Center of the World", repairing and modifying combat vehicles. The facility was renamed the Anniston Army Depot (ANAD) in 1962, and continued with the unending process of upgrading combat vehicles to modern standards. This started with the tanks of the 1950s, the Patton tank, continued to the M1 Abrams, the Stryker, and a variety of other armored and heavy vehicles.

About this time, ANAD began to be used as housing for the storage of Cold War-era chemical-warfare munitions. In the later 1960s and 1970s a chemical disposal process was begun, which has taken decades to execute. Since very early in this disposal process, Anniston Depot has pursued an environmental goal in excess of even modern Federal minimum standards.

Presently, Anniston Army Depot is a complex industrial center known for superb maintenance and repair of multi-million dollar military vehicles, equipment, ammunition, and missiles. It is home to tenant organizations such as the Defense Distribution Depot Anniston Alabama (DDAA), the Anniston Defense Munitions Center (ADMC), the Anniston Chemical Activity (ANCA), and the Center of Military History Clearing House.