As the 49th Troop Carrier Squadron, it flew Douglas C-47 Skytrains in the Mediterranean Theater of Operations during World War II, earning Distinguished Unit Citations for carrying reinforcements to Sicily despite fire from ground and naval forces in July 1943, and for participation in Operation Overlord in June 1944.

[4] Although the 49th did not take part in the first airdrop of Operation Husky, the Allied invasion of Sicily,[5] two days later, 11 July 1943, the squadron was part of a formation of troop carrier units of the 52d Troop Carrier Wing bringing reinforcements, planning to drop paratroops near Gela.

Mistaking the troop carriers for another enemy attack, ships of the assault force and antiaircraft units ashore began a heavy fire on squadron's C-47s as they departed.

[1] In February 1944, the squadron moved to RAF Folkingham, England, where it became part of IX Troop Carrier Command and began training for the assault on the continent of Europe.

[4] On 17 September, the squadron participated in Operation Market Garden, the airborne assault on the Netherlands, when it dropped troopers near Arnhem and Nijmegen.

In February 1945, the squadron moved to Achiet Airfield in France, where it began converting to Curtiss C-46 Commandos in preparation for Operation Varsity, the airborne assault across the Rhine.