During World War II, she participated in numerous patrols and sorties into the Mediterranean, both to escort Italian convoys to North Africa and in attempts to catch the British Mediterranean Fleet. In November 1940, the British launched an air raid on Taranto; "Caio Duilio" was hit by one torpedo launched by a Fairey Swordfish torpedo bomber, which caused significant damage. Repairs lasted some five months, after which the ship returned to convoy escort duties. A fuel shortage immobilized the bulk of the Italian surface fleet in 1942, and "Caio Duilio" remained out of service until the Italian surrender in September 1943. She was thereafter interned at Malta until 1944, when the Allies permitted her return to Italian waters. She survived the war, and continued to serve in the post-war Italian navy, primarily as a training ship. "Caio Duilio" was placed in reserve for a final time in 1953; she remained in the Italian navy's inventory for another three years before she was stricken from the naval register in late 1956 and sold for scrapping the following year.