On 20 October 1944, U.S. Forces landed on the Island of Leyte, the first of the Japanese-held Philippine Islands to be invaded. In response, the Japanese Navy activated the complex "Sho-Go" Operation, in which several different surface and air forces would converge on the Philippines to try and drive off the Americans. As part of Vice Admiral Takeo Kurita's Center Force, Yamato moved up to Brunei Bay, Borneo, to refuel and then steamed toward the operational area in company with four other battleships, ten heavy cruisers and numerous other warships. On 23 October, while west of the Philippines, the Center Force was attacked by the U.S. submarines Darter (SS-227) and Dace (SS-247). Three heavy cruisers were torpedoed and two sunk, including Kurita's flagship, Atago. The Admiral then moved to Yamato, which served as his flagship for the rest of the operation.

The next day, 24 October, as the Center Force steamed through the Philippines' central Sibuyan Sea, it was repeatedly attacked by planes from U.S. aircraft carriers. Battleship Musashi was sunk and a heavy cruiser forced to retire. Yamato and several other ships were hit but remained battleworthy. The Americans thought the entire Center Force had retreated, but it transited the San Bernardino Strait under cover of darkness and entered the Pacific.

In the morning of 25 October, while off Samar, Kurita's Center Force encountered a U.S. Navy escort aircraft carrier task group. In a long running battle, in which Yamato fired her big guns at enemy ships for the only time in her career, one U.S. carrier and three destroyers were sunk. Fiercely opposed by the escort carriers' planes and the destroyers' guns and torpedoes, Vice Admiral Kurita lost three heavy cruisers, and his nerve. Though the way was almost clear to move onward to Leyte Gulf, where a climactic battleship gunnery duel would have certainly resulted, he ordered his force to withdraw and return to Brunei Bay. That ended Yamato's participation in the last great naval battle of World War II, and marked the end of the Japanese Fleet as a major threat to Allied offensive operations in the Western Pacific.