The battalion's first experience of combat came during an attack against the Italian garrison at Giarabub in March 1941. This was followed by defensive actions during the Siege of Tobruk later in the year before the 2/10th joined the Allied garrison in Syria, which had previously been captured from the Vichy French. In early 1942, following Japan's entry into the war, the 2/10th was withdrawn to Australia and in August 1942, at the height of the Japanese advance in the Pacific, the battalion was committed to the fighting around Milne Bay in the Territory of Papua, suffering heavy casualties in their debut in the Pacific. Further fighting came during the Battle of Buna–Gona in northern Papua before the 2/10th was brought back to Australia for re-organisation in March 1943. In August 1943, it was sent to the Territory of New Guinea, first undertaking jungle training near Port Moresby and then, in December 1943, moving inland into the Finisterre Mountains where they later fought the Battle of Shaggy Ridge. After being withdrawn to Australia in mid-1944, the battalion did not take part in further fighting until the final months of the war when they were committed to the fighting on Balikpapan in July 1945. Following the conclusion of hostilities, the 2/10th Battalion was disbanded in December 1945.