First patrol, August ? October 1942
On 23 August 1942 Wahoo got underway for her first war patrol, seeking Japanese shipping in waters west of Truk, particularly in the area between the Hall Islands and the Namonuito Atoll. On 6 September, her third day in the area, Wahoo fired three torpedoes at her first target, a lone freighter; all torpedoes missed because the ship turned toward Wahoo, apparently with the intent to ram. The submarine dodged, fearful of counterattack from the air.
She continued to patrol the Truk area until 20 September when she decided to leave the southwest part of the patrol area and explore south of the Namonuito Atoll. Under a bright moon and clear sky, the submarine sighted a freighter and her escort. Wahoo launched three torpedoes; all missed. A fourth hit the target, which was thought to take a port list and settled by the stern. Four minutes later, a series of three underwater explosions wracked the freighter. Wahoo was chased by the escort but escaped by radically changing course in a rain squall. Though credited at the time with a freighter of 6,400 tons, postwar analysis of Japanese shipping records by JANAC showed no sinking at this time or place.
Wahoo continued her patrol and sighted several airplanes, a patrol boat, and a tender but was unable to close on any possible targets. On 1 October 1942, the submarine extended her patrol to Ulul Island, where she sighted several fishing boats. Within the next few days, Wahoo missed two of the best targets of the war. The first was Chiyoda (listed as a seaplane tender, she was in fact a mother ship to midget submarines), sailing without escort; Wahoo proved unable to reach a firing position. On 5 October, she sighted an aircraft carrier, believed to be Ryûjô, escorted by two destroyers. (In fact, Ryûjô had been sunk six weeks earlier in the Solomon Islands). Due to an approach lacking aggressiveness and skill, the target sailed away untouched. Two days later, Wahoo departed the patrol area. On 16 October, she made rendezvous with her escort and proceeded to Pearl Harbor, where she ended her first patrol on 17 October 1942.
She commenced refit the following day alongside submarine tender Sperry (AS-12). Wahoo then shifted to Submarine Base Pearl Harbor for overhaul. There, a 4 in (100 mm) gun and two 20 mm guns were installed. Overhaul was completed on 2 November and, after three days' training, Wahoo was again ready for sea.