After training in the United States, the squadron deployed to the Mediterranean Theater of Operations, where it participated in the strategic bombing campaign against Germany.

In August 1946, the squadron deployed to Ladd Field, Alaska Territory, where it conducted long range aerial reconnaissance over the Arctic.

The 46th squadron flew "Project Nanook" to assess the Soviet threat in the Arctic at the beginning of the Cold War.

[1] The squadron assembled at its combat station, Grottaglie Airfield in Southern Italy, in early January 1944, from which it operated primarily on strategic bombing missions.

It attacked oil refineries, communications centers, aircraft factories and industrial facilities in Italy, Germany, Czechoslovakia, Hungary, Romania, Albania and Greece.

The attacking group was heavily outnumbered by German interceptor aircraft, but not only succeeded in destroying its assigned target, but inflicted heavy losses on the defending fighters.

[4] The squadron attacked gun emplacements to support Operation Dragoon, the invasion of southern France in August 1944.

It attacked troop concentrations, bridges and viaducts during Operation Grapeshot, the Fifteenth Army Group offensive in Northern Italy in the spring of 1945.

[1][4] The squadron reformed at Sioux Falls Army Air Field, South Dakota at the end of May.

[1] Its new mission was to provide very long range reconnaissance as part of the newly established Strategic Air Command (SAC).

Exploratory flights were made to obtain information necessary to establish commercial airline service over the Arctic.