October 1944, the Combined Fleet ordered the activation of Operation Shō-Gō 1, the defense of the Philippine Islands, in anticipation of an American invasion of the islands. I-46 departed Kure, Japan, to begin her first war patrol and take part in Shō-Gō 1, assigned a patrol area east of Leyte in the Philippines as part of the "B" Group. Her patrol area was the westernmost of those assigned to the submarines of her group, and was adjacent to the area assigned to the submarine . On 20 October 1944, the Battle of Leyte began with U.S. landings on Leyte. In response, major units of the Imperial Japanese Navy converged on Leyte, resulting in the Battle of Leyte Gulf, which lasted from 23 to 26 October 1944. On 24 October, the 6th Fleet ordered eleven submarines, including I-46, to converge in an area extending from Samar to Surigao Strait. While I-46 was operating east of Leyte on 25 October 1944, a U.S. patrol plane forced her to dive at 06:45. A ship she identified from its propeller noises as a destroyer pursued her for the next eleven hours, during which she heard over 200 distant depth charge explosions. On 26 October 1944, I-46 transmitted a report that she had sighted a small Allied convoy east of her patrol area. She was never heard from again. When the 6th Fleet ordered her to move to a new patrol station east of Leyte on 27 October 1944, she did not acknowledge it. Loss The circumstances of I-46′s loss remain unknown. At 12:18 on 28 October 1944, the destroyers and detected a submarine attempting to penetrate the screen of United States Navy Task Group 38.4 — which included the aircraft carriers , , , and — east of Leyte. While the aircraft carriers steered away from the submarine contact at high speed, Gridley made three depth charge attacks against the submarine and Helm made four. After Helm′s fourth attack, which took place at 14:11, a large explosion followed by two smaller ones occurred. Oil and air bubbles appeared on the surface, and damaged deck planking and human remains were recovered after the attack. The submarine sank at . On both 30 October and 1 November 1944, , I-46, and I-54 all failed to make scheduled daily 19:00 status reports. On 2 December 1944, the Imperial Japanese Navy declared I-46 to be presumed lost east