In August 1940 Iachino was given command of the 2ndNaval Squadron, with flag on the heavy cruiserPola, after its previous commander, Admiral Riccardo Paladini, came down with angina pectoris. In this role, he participated on 27 November 1940 in the Battle of Cape Spartivento. On 9 December 1940 he replaced Admiral Inigo Campioni as commander of the entire battle fleet of the Regia Marina, with flag on the battleship Vittorio Veneto. On 9 February 1941, Iachino led the Italian fleet in the unsuccessful pursuit of the British Force H, after the latter had bombarded Genoa and La Spezia. He again commanded the Italian battle fleet in the Battle of Cape Matapan, which resulted in the biggest defeat ever suffered by the Regia Marina; dismissing reports of nearby British battleships as incorrect or exaggerated, he sent the entire 1st Cruiser Division to the rescue of the stricken cruiser Pola, resulting in the annihilation of the entire Division by the three battleships of Admiral Andrew Browne Cunningham's Mediterranean Fleet. His actions during this battle have been the subject of much criticism since then; despite this, Iachino wasn't relieved of command. In July and September 1941 Iachino led the fleet in fruitless attempts to intercept British convoys to Malta. During the First Battle of Sirte and the Second Battle of Sirte the forces under his command clashed with the escorts of British convoys heading for Malta, but despite his superior strength Iachino - concerned about not underestimating the enemy forces and avoiding night action, both of which had been his fatal mistakes at Matapan - did not press the attack and was unable to cause significant damage to the convoys. Operation Vigorous was instead his most important success; despite the losses caused by air and submarine attacks, he kept advancing towards the British convoy sailing from Alexandria to Malta, eventually leading to it aborting its mission and turning back to port. On 5 April 1943 Iachino was replaced by Admiral Carlo Bergamini as the commander of the Italian battle fleet. At the same time he was promoted to Ammiraglio d'Armata. In 1945 he was transferred to the reserve, but he appealed against this and was restored to active service in 1948. He finally left active service in 1954 and was discharged in 1962. During his later years he wrote several books about his actions during the war, especially focusing on Matapan and trying to justify his actions in that battle. In 1974 he donated the money for the construction of a Sailor's Monument in Taranto. He died in Rome on 3 December 1976, at the age of 87.