The 322nd Bombardment Squadron (Medium) was activated on 19-Jun-1942 at MacDill Field, Florida with B-26B Marauder aircraft. In late September 1942 the unit moved to Drane Field, Florida. The Ground echelon sailed for the UK aboard the Queen Elizabeth on 24-November-1942 arriving in Greenock, UK on 30-Nov-42. The ground unit was originally to be stationed at Bury St. Edmunds, but the field was undergoing improvement modifications so they went to Rattlesden until 22-May-1943. The 450th Bomb Squadron moved to Morrison Field on 6-February-1943 and left for Bury St. Edmunds by the southern ferry route arriving 7-9 March-1943. The 452nd Bomb Squadron followed in late March 1943; the 451st and 449th Bomb Squadrons followed in April and May 1943. The last aircraft arrived at Bury St. Edmunds on 29-May-1943.

Between 14-May-1943 and 8-October-1943 the Group flew 34 missions and lost 13 aircraft MIA. A low-level strike mission was flown by the 322nd Bomb Group on 14 May 1943, the first to fly B-26 Marauders from the UK. Only three days later another low-level mission over Holland resulted in the loss of ten out of eleven aircraft and sixty crew, when bombers were brought down by flak and interceptors. In the aftermath of this shocking loss, the Group trained for medium-altitude operations for several weeks, resuming combat missions on 17 July 1943.

On 16-October-1943 the Group was reassigned to the Ninth Air Force but continued to be based in England, at Andrews Field (Great Saling), Essex until September 1944 when they moved to a succession of bases in France and Belgium.