The idea of a NATO Defense College originated with General Dwight D. Eisenhower, the first Supreme Allied Commander Europe, who identified very early on the need for a new international institution with a unique education mission.

On 10 September 1999, the new College building, twice the size of the old one, was inaugurated in Cecchignola Città Militare, a military zone 2 km from the former site.

Based on Strategic Guidance issued to the NDC by the North Atlantic Council and the NATO Military Committee (MC123/8), the NDC's stated mission is to: There is a high priority requirement to develop individuals, both on the military and on the civilian side, who will have a thorough grasp of the many complicated factors which are involved in the problem of creating an adequate defense posture for the North Atlantic Treaty area.

In July 2023, Lieutenant-General Max Arthur Lund Thorsø Nielsen of the Royal Danish Air Force assumed command.

The Director of Enablement (a Brigadier General) supervises management of the NDC's financial and technical resources with the aim of improving the quality of life in the college and creating the best conditions for work and study.

The formal aims of the International Week are: Was established in 1999 at the Washington Summit as a Consortium of the Willing and founded in the spirit of Partnership for Peace (PfP).