After the disestablishment of the Manhattan Engineering District (MED) in 1947, AFSWP was formed to provide military training in nuclear weapons' operations.

[7]DTRA employs approximately 1,400 DoD civilians and 800 uniformed service members at more than a dozen permanent locations worldwide.

The remaining 15% of the workforce is stationed in Germany, Kazakhstan, Azerbaijan, Uzbekistan, Georgia, Ukraine, Armenia, Kenya, South Korea, Japan, and Singapore.

DTRA also has liaisons with the U.S. military's Combatant Commands, the National Guard Bureau, the FBI and other U.S. government interagency partners.

DTRA has spent approximately $300 million on scientific R&D efforts since 2003, developing vaccines and therapeutic treatments against viral hemorrhagic fever, including Ebola.

Starting in 2007, DTRA partnered with the National Institute of Allergy and Infectious Diseases (NIAID) of the United States Department of Health and Human Services and the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) to fund research on the drug now called ZMapp, which has since been used on several patients.

[19][20] The Nunn-Lugar Cooperative Threat Reduction program provided for the DTRA to award a $4 million contract to MRIGlobal to "configure, equip, deploy and staff two quick response mobile laboratory systems (MLS) to support the ongoing Ebola outbreak in West Africa."

[24][25] DTRA was one of the key United States Department of Defense agencies that developed the Field Deployable Hydrolysis System (FDHS) used to destroy Syria's chemical weapons aboard the U.S.-flagged container ship MV Cape Ray in the summer of 2014[26][27] after Syria agreed to give up its chemical weapons stockpile under international pressure and in accordance with United Nations Security Council Resolution 2118.

[30] DTRA funded, managed, and tested the Massive Ordnance Penetrator (MOP) bomb until February 2010, when the program was turned over to the USAF.

DTRA developed the MOP to fulfill a long-standing Air Force requirement for a weapon that could destroy hard and deeply buried targets.

Code-named Project MAXIMUS, DTRA, and the United States Department of Energy moved 1.77 metric tons of LEU and approximately 1,000 highly radioactive sources out of Iraq by the summer of 2004.

Shortly afterwards, the COVID-19 pandemic began, and DOMANE started researching existing, pre-approved medications like Pepcid (famotidine) for potential cost-effective treatments for COVID-19.