The 358th flew the first mission for the group on November 17, 1942. The group would become one of the legendary units of the Eighth Air Force. Initially missions were conducted against targets such as aerodromes, railways, and submarine pens in France until 1943, then flying missions into Germany itself. The 303d took part in the first penetration into Germany by heavy bombers of Eighth Air Force by striking the U-boat yard at Wilhelmshaven on January 27, 1943 then attacked other targets such as the ball-bearing plants at Schweinfurt, shipbuilding yards at Bremen, a synthetic rubber plant at Huls, an aircraft engine factory at Hamburg, industrial areas of Frankfurt, an aerodrome at Villacoublay, and a marshalling yard at Le Mans.
The 303d received a Distinguished Unit Citation for an operation on January 11, 1944 when, in spite of continuous attacks by enemy fighters in weather that prevented effective fighter cover from reaching the group, it successfully struck an aircraft assembly plant at Oschersleben.
The group attacked gun emplacements and bridges in the Pas de Calais area during the invasion of Normandy in June 1944; bombed enemy troops to support the breakthrough at St Lo in July 1944. It struck airfields, oil depots, and other targets during the Battle of the Bulge, and bombed military installations in the Wesel area to aid the Allied assault across the Rhine in March 1945.
The last mission for the 303d was flown on 25 April 1945 when it attacked an armament works in Pilsen. During its combat tour the group flew 364 missions comprising 10,271 sorties, dropped 26,346 tons of bombs and shot down 378 enemy aircraft with another 104 probably downed. The group also saw 817 of its men killed in action with another 754 becoming prisoners of war.