[4] Equipped with new Spad XIIIs, the 49th began flying operations with the First Army and was credited with participation in the Lorraine, St Mihiel, and the Meuse-Argonne campaigns.

Participated in demonstrations of effectiveness of aerial bombardment on warships, June–September 1921; mercy mission in relief of marooned inhabitants of islands in the frozen Chesapeake, 9–11 February 1936.

[5] Began its association with testing when it received the first of the five Boeing YB-9, first all-metal monoplane bomber aircraft designed for the United States Army Air Corps, on 14 September 1932.

The trip to Buenos Aires represented the longest distance performance of its kind on record and won the 2nd Bombardment Group the Mackay Trophy in 1938.

Following 24 January 1939 Chillán earthquake in Chile, the XB-15, a prototype aircraft that had been assigned to the squadron to test the feasibility of operating very heavy bombers, flew a relief mission carrying medical supplies.

Commanded by Major Caleb V. Haynes, the aircraft carried 3,250 lb (1,470 kg) of American Red Cross emergency supplies to Santiago, making only two stops along the way, at France Field in the Panama Canal Zone, and at Lima, Peru.

Some of the important missions the 49th participated in were: the monastery at Monte Cassino, Italy, on 15 February 1944; enemy troop concentrations at Anzio beachhead on 2 March 1944; and the oil refineries at Ploiești, Romania, throughout the spring of 1944.

By the time the 49th was inactivated, it participated in 412 combat missions flown over Africa, France, Germany, Italy, Austria, Bulgaria, Yugoslavia, Romania, and Hungary.

The squadron soon moved to Davis–Monthan Field, Arizona, and received training on the Boeing B-29 Superfortress as part of the new Strategic Air Command long-range strike force.

In September 1950, the squadron moved to Hunter Air Force Base, Georgia and began flying training missions over the eastern half of the United States.

The 49th returned home to perform alert duties during the Cuban Missile Crisis of 1962 before moving to Barksdale Air Force Base, Louisiana.

[5] May 2019 saw the 49th Test and Evaluation Squadron deploy a B-52H to Joint Base Pearl Harbor-Hickam for a demonstration of Quickstrike-ER (QS-ER) naval mines on the Pacific Missile Range Facility, Hawaii.

The QS-ER combines Joint Direct Attack Munitions (JDAM) technology and an additional wing kit and battery section with existing mine components.