Cero cleared New London 17 August 1943 for Pacific waters, and on 26 September sailed from Pearl Harbor, bound for the East China and Yellow Seas on her first war patrol.

After refitting at Midway from 16 November to 13 December 1943, Cero, Edward Dissette commanding, made an unproductive second war patrol along the Truk-New Ireland route, then put into Milne Bay, New Guinea, from 12 January to 4 February 1944.

On 11 April 1944, a United States Army Air Forces B-24 Liberator bomber mistakenly strafed and bombed Cero as she submerged in the western Pacific Ocean about 300 nautical miles (560 km; 350 mi) east-northeast of Biak Island.

Cero was refitted at Seeadler Harbor, Manus, from 2 to 26 June 1944, then put to sea for the dangerous waters off Mindanao, where on 5 August, she sent another tanker to the bottom; fifteen days later she finished her fifth patrol at Brisbane.

Although not permitted by her orders to attack escorted merchantmen while on this mission, Cero encountered two small craft on 27 October, and in a resulting gun action, damaged both and forced them ashore.

Cruising off Honshū and Hokkaidō, she not only provided lifeguard services for air strikes on Japan, but sank two picket boats and damaged a third, as well as sending three freighters and a large trawler to the bottom.