The VI Corps took part in some of the most high profile operations in World War II. Its first combat was during the Allied invasion of Italy when it landed at Salerno with the British X Corps under Fifth Army as part of Operation Avalanche. The stiffness of the German defences sorely tested VI Corps and it suffered heavy casualties before German attempts to throw the Allied force back into the sea were thwarted by a combination of naval gunfire, bombing and the approach of British Eighth Army from the south. The commander of the corps was replaced after Salerno, as he was judged to be worn out.

VI Corps then joined in the pursuit of German forces up the Italian peninsula. However, the Germans turned and fought at the Winter Line, and the Corps became involved in heavy fighting to try to break through. The first attempts failed, however VI Corps was taken out of the line in an attempt to find a solution to the problem. In its second amphibious assault of the war, it went ashore at Anzio in Operation Shingle in January 1944. At first German resistance was negligible. However, General John P. Lucas, the general commanding the corps felt he needed to consolidate his beachhead before breaking out. This gave the Germans critical time to concentrate forces against him. Another bloody stalemate ensued, with the Corps almost being driven back into the sea for the second time in Italy, again being rescued by naval and air power. When the statemate was finally broken in the spring of 1944, the Corps had lost another commander; Lucas was sacked for his poor performance and replaced by Major General Lucian Truscott.

When the Corps broke out, it was ordered to do what many considered a very questionable act. Instead of blocking the line of German retreat, it was sent pell-mell towards Rome. General Mark W. Clark, the commander of Fifth Army got the glory of capturing the Italian capital city, but was castigated by his peers and superiors for failing to trap and destroy the German forces. This, along with the poor perforamnce at Anzio would cast a shadow over the reputation of the Corps.

Following the capture of Rome, VI Corps again left the line, and again prepared for an amphbious assault, its third and last of the war. Operation Dragoon was aimed at capturing the south of France, and VI Corps provided the assault troops, coming under Seventh Army. The landing was not opposed with much fervour, and VI Corps swept up the Rhone valley to join forces with Eisenhower's troops coming from Normandy. VI Corps spent the rest of the war as part of Seventh Army, operating on the southern end of the Allied front against the Germans in the west. It ended the war in southern Germany.