[2] As the Imperial Japanese Navy began to deploy for the upcoming conflict in the Pacific, Submarine Squadron 1 was assigned to the Advance Force, and I-15 departed Yokosuka, Japan, on 21 November 1941 in company with the submarines I-9, I-17, and I-25, bound for the waters of the Hawaiian Islands to participate in Operation Z, the Japanese attack on Pearl Harbor that would bring Japan and the United States into World War II.

[2] On 13 December 1941, Japanese Imperial General Headquarters ordered the submarines of the 6th Fleet to bombard the United States West Coast.

[2] She surfaced off the Farallons around midnight on the night of 17–18 December 1941 to recharge her batteries, and her commanding officer permitted her crew to come on deck to see the lights of San Francisco, California, which were visible to the south.

[2] On 1 February 1942, planes from the U.S. Navy aircraft carrier USS Enterprise (CV-6) raided Kwajalein, and I-9, I-15, I-17, I-19, and I-25 submerged to the harbor bottom at a depth of 150 feet (46 m) to avoid attack.

[3] I-23 was to patrol south of Hawaii to provide weather reports and an air-sea rescue capability if either or both of the flying boats were forced down,[3] while I-9, which remained at sea without returning to Kwajalein, was to operate in an area halfway between Wotje Atoll and the French Frigate Shoals to transmit a radio beacon signal to help the flying boats navigate during the first leg of their flight.

[3] On 5 February 1942, I-15 arrived at Kwajalein, where she, I-19, and I-26 disembarked their Yokosuka E14Y (Allied reporting name "Glen") floatplanes to make room for six fuel tanks each in their hangars for the storage of aviation gasoline with which to refuel the flying boats.

[2] The two aircraft soon took off again, and in the predawn hours of 5 March 1942 dropped eight 250-kilogram (551 lb) bombs over Honolulu, inflicting little damage and no casualties due to the overcast conditions, before flying back to the Marshall Islands.

[2] While I-15, I-19, I-25, and I-26 were in drydock at Yokosuka, 16 United States Army Air Forces B-25 Mitchell medium bombers launched from the aircraft carrier USS Hornet (CV-8) struck targets in Japan on 18 April 1942 in the Doolittle Raid.

[2] One B-25 bombed and damaged the light aircraft carrier Ryūhō, which was undergoing conversion from the submarine tender Taigei in a nearby drydock.

[2] Submarine Division 2, consisting of I-15, I-17, and I-19, received orders to proceed to the waters east of the Solomons, and I-15 got underway from Yokosuka accordingly on 15 August 1942 to begin her third war patrol.

On 26 August, the Advance Force ordered I-15, I-17, I-19, I-26, and the submarines I-11, I-33, I-174, and I-175 to deploy from the south to the east of San Cristobal in the southeastern Solomons to interdict American supplies and reinforcements for Guadalcanal.

[2] On 13 September, an H8K flying boat reported an Allied task force 345 nautical miles (639 km; 397 mi) south-southeast of Tulagi, and I-9, I-15, I-17, I-21, I-24, I-26, I-33, and the submarine I-31 received orders to form a patrol line to intercept it.

[2] Reassigned to the 2nd Reconnaissance Unit — and later directly to Submarine Squadron 1 — I-15 departed Truk on 5 October 1942 to begin her fourth war patrol.

[2] She arrived in Indispensable Strait in the Solomon Islands on 12 October, and that day refueled an Imperial Japanese Navy Aichi E13A1 (Allied reporting name "Jake") floatplane of the "R" Area Air Force based at Shortland Island and Rekata Bay;[2] the aircraft sighted a U.S. Navy task force centered around the aircraft carrier Hornet east of Malaita on the morning of 13 October.

[2] Operating 200 nautical miles (370 km; 230 mi) west of Espiritu Santo at 03:50 on 27 October, I-15 sighted a large U.S. task force steaming south from the Santa Cruz Islands.

[2] During a voyage from Espiritu Santo to Guadalcanal with a cargo of supplies, the U.S. Navy fast minesweeper USS Southard (DMS-10) sighted I-15 on the surface recharging her batteries off Cape Recherche on San Cristobal at 02:30 on 10 November 1942.

[2] Damage from the depth-charge attacks forced I-15 to surface at the south end of Indispensable Strait at 10:03, and Southard opened gunfire on her at a range of 2,000 yards (1,830 m).