The organization was the first newly established Numbered Air Force (NAF) by the USAF after World War II.

It later became a provisional Air Expeditionary Task Force under USAFE as part of the Global War on Terrorism.

Existing Spanish Air Force bases near Madrid, Sevilla, and Zaragoza were expanded to accommodate the 16 AF.

The 401st Tactical Fighter Wing, with three squadrons of F-100D Super Sabres, moved from the United States to Torrejon Air Base, Spain.

In 1961, General David Wade was dispatched to Torrejón, where he took command of SAC's 16th Air Expeditionary Task Force.

Sixteenth Air Force aircraft participated in the raid on the Bosnian-Serb held airfield at Udbina in November 1994.

Headquarters 16 AF formed the joint force air component command for Operation Silver Wake, the evacuation of Americans and allied non-combatants from Albania.

The 39th Wing at Incirlik AB, Turkey, deployed a flying ambulance surgical team to Dhahran Air Base, Saudi Arabia in response to the Khobar Towers bombing.

In 2005, the Sixteenth Air Force moved to Ramstein AB, Germany to become USAFE's new Warfighting Headquarters.

It supported approximately 11,000 Air Force and civilian members at two main operating bases, four support bases and other sites in Spain, France, Germany, Italy, Croatia, Kosovo, Bosnia-Herzegovina, Hungary, Macedonia, Greece, and Turkey, and conducted peacetime engagement throughout the region.