Established as the Southeast Air District on October 19, 1940 and activated on December 18, 1940 at MacDill Field, Florida, the unit provided coastal defense of the United States before the war began. Within a few months, it was redesignated 3rd Air Force on March 26, 1941 and later as Third Air Force on September 18, 1942.

At the outbreak of World War II, Third Air Force took on the additional role of aircrew training. Between December 1941 and August 1945, Third Air Force trained 856 combat units - consisting of 18,894 officers and 168,733 enlisted personnel. Third Air Force units - based throughout the war in the United States - also participated in anti-submarine patrols, earning an antisubmarine campaign streamer in addition to the American Theater streamer.

Third Air Force inactivated on November 1, 1946, and remained so until May 1, 1951, when it replaced Third Air Division at RAF South Ruislip in the United Kingdom (UK). This would not be the only change to face the command over the years. In 1953, British civilians replaced U.S. Air Force support personnel at several bases. The next year saw 10 bases closed and returned to the UK Ministry of Defence.

Further consolidations and reductions closed bases every year from 1961 to 1965. Another significant change to Third Air Force occurred in 1961, when U.S. Air Forces in Europe (USAFE) gave operational control of Third Air Force units to Seventeenth Air Force. Third Air Force then concentrated on base support and its role with the British government. However, the transfer of 1961 had proven too difficult on unit command and control to sustain, so by 1963, USAFE returned operational control of UK units to Third Air Force. The unit's headquarters moved from RAF South Ruislip to RAF Mildenhall in 1972 in order to enhance combat readiness of its units.

Considerable changes occurred in the 1980s. In 1982, two ground-launched cruise missile (GLCM) units activated at RAF Greenham Common and RAF Molesworth. The placement of GLCMs at the two bases resulted in numerous protests that sparked heated debate throughout the UK.

On the night of April 14, 1986, Third Air Force launched the first U.S. combat operation from the United Kingdom since 1945. The target was Libya. Eighteen RAF Lakenheath F-111Fs struck targets at Benghazi, Azziziyah, and Sidi Bilal. The EF-111As from RAF Upper Heyford provided tactical jamming support during the raid, while tankers stationed at RAF Mildenhall and RAF Fairford provided aerial refueling.

In December 1987, just as the last GLCM unit reached initial operational capability, the United States and the Soviet Union concluded an arms control agreement that eventually eliminated the GLCM system. In 1988, Third Air Force had nine major units and 10 main operating bases. Six years later, it had only two main operating bases, one standby base, and a handful of geographically separated units.

In 1996, two more important changes took place for Third Air Force. During that year, the USAFE commander decided to inactivate Seventeenth Air Force and transfer its units to Third Air Force. At the same time, USAFE reoriented its two remaining numbered air forces. While Sixteenth Air Force focused on wartime operations (primarily in the Balkans), Third Air Force was assigned the task of operations short of war with a primary focus on Africa. During that first year, Third Air Force participated in three African operations, the largest being GUARDIAN ASSISTANCE, a relief effort in Rwanda. In 1997 and 1998, Third Air Force personnel deployed to Africa four more times, once as the lead for a joint task force to support then-President Bill Clinton's historic visit to Africa.

In 1999, Third Air Force became the lead element for Operation SHINING HOPE, the U.S. military's humanitarian operation in Albania. The headquarters provided support in bedding down additional forces brought into the UK and supported NATO operations against Yugoslavia. Third Air Force's wings provided the bulk of U.S. combat forces in the Balkan conflict, flying combat missions from their home stations.

In 2005, USAFE once again realigned its numbered air forces. Sixteenth Air Force aligned as the command's new Warfighting Headquarters and Third Air Force inactivated on November 1, ending the unit's prestigious 54 year legacy in the UK.

Just over a year later, Third Air Force activated again on December 1, 2006, at Ramstein AB, Germany, as the USAFE component numbered air force supporting U.S. European Command (EUCOM). It was responsible for supporting the EUCOM commander's strategic objectives across the full range of military operations. When a joint task force is created under EUCOM, the Third Air Force commander is ready to assume the roles of Joint Forces Air Component Commander and Commander Air Forces, or lead the JTF as a Joint Force Commander.

From 2011 to 2012, USAFE reorganized its numbered air forces again by consolidating Third Air Force and Seventeenth Air Force (activated again on October 1, 2005) directorates within HQ USAFE. On 20 April 2012, Third Air Force assumed responsibility as the numbered air component for U.S. Africa Command (AFRICOM) when Seventeenth Air Force inactivated. In addition, the Third Air Force staff in the UK aligned under USAFE, and redesignated from Third Air Force-UK to USAFE-UK. Finally, the 617th Air Operations Center (AOC) was consolidated with the 603rd AOC, retained the 603rd AOC designation, and supported the EUCOM and AFRICOM areas of responsibility until realigned under USAFE on October 20, 2017.

Today, Third Air Force plans, executes and assesses a full spectrum of airpower operations and consists of its headquarters operations directorate and 10 wings totaling more than 31,000 personnel.