In April 1941, Ito became chief of staff of the Combined Fleet, and in September, he was appointed vice chief of the navy General Staff under Admiral Nagano Osami. He was promoted to vice admiral that October and played a key role in the development of Japanese naval strategy in the Pacific war. Reluctant to see Japan go to war against the United States, he opposed the Pearl Harbor attack, but Admiral Yamamoto Isoroku, commander of the Combined Fleet, urged Nagano to authorize the plan. On 1 December 1941, with the fleet already at sea, Ito ordered the attack on Pearl Harbor. He held his staff post for more than three years, but he desired a naval command.
In December 1944, he was appointed to command the Second Fleet. The Japanese navy had already been crushed in the Battle of Leyte Gulf the previous October, and Ito's fleet was the only operative Japanese navy force. On 5 April 1945, Admiral Toyoda Soemu ordered Operation ten-go, whereby Second Fleet would join the battle for Okinawa, which had recently been invaded by U.S. forces. This operation was so reckless that Ito refused the order. His fleet lacked both aircraft carriers and aircraft, which were essential to protect its ships from air attack. Moreover, the fleet would be provided only enough fuel for a one-way trip from Kyushu to Okinawa. It was obvious to Ito and others that Toyoda intended to send the 7,000 men of the fleet on a suicide mission.
Ultimately, Vice Admiral Kusaka Ryunosuke prevailed on him to obey the order, and on 6 April, Ito set out with the battleship Yamato and eight destroyers. The plan called for the Yamato to fight its way to the U.S. invasion site, destroy as many American ships as possible, and then beach itself to act as a stationary battery. On 7 April 1945, the Second Fleet ships were attacked by U.S. Vice Admiral Marc A. Mitscher's Fast Carrier Task Force 58 in the East China Sea, and the Yamato was sunk, along with Ito and 3,700 of her crew. Kotani Ken
Morison, Samuel Eliot. History of United States Naval Operations in World War II. Vol. 5, The Struggle for Guadalcanal, August 1942–February 1943. Boston: Little, Brown, 1949.; Yoshida Mitsuru. Requiem for Battleship "Yamato." Trans. Richard Minear. Seattle: University of Washington Press, 1985.; Yoshida Mitsuru. Teitoku Ito Seiichi no Syogai ([The life of Admiral Ito Seiichi). Tokyo: Bungeishunjyu, 1986.