Activated in the summer of 1942 under I Troop Carrier Command and equipped with Douglas C-47 Skytrains at Drew Field, FL.

Deployed to French Morocco in May 1943 and assigned to Twelfth Air Force to support combat operations in the North African Campaign.

Reassigned to IX Troop Carrier Command in England during early 1944 as part of the build-up of Allied forces prior to Operation Overlord, the invasion of France.

The squadron also hauled food, clothing, medicine, gasoline, ordnance equipment, and other supplies to the front lines and evacuated patients to rear zone hospitals.

It dropped paratroops near Nijmegen and towed gliders carrying reinforcements during the Operation Market Garden, the airborne attack on the Netherlands.

Following the horrors of Hurricane Katrina, 50th aircrews helped relocate survivors from the New Orleans, Louisiana and Biloxi, Mississippi areas to Little Rock, Arkansas.

A ceremony marking the reactivation of the squadron was held at MacDill Air Force Base, Florida on 2 October 2017.