[4] On 8 February 1943, Ro-101 departed Truk to begin her first war patrol, assigned a patrol area east of Port Moresby, New Guinea, to provide distant cover for Operation Ke, the Japanese evacuation of their forces on Guadalcanal[4] which brought the Guadalcanal campaign to an end after six months of fighting.

[4] He decided to wait for dark to attack, but when the ship put on speed and headed off in the direction of Port Moresby, Ro-101 lost contact with it.

[4] In the Battle of the Bismarck Sea, fought between 2 and 4 March 1943, United States Army Air Forces and Royal Australian Air Force aircraft and United States Navy PT boats annihilated a Japanese convoy in the Bismarck Sea that was attempting to carry the Imperial Japanese Army's 51st Division to Lae on New Guinea, sinking all eight ships of the convoy and four of the eight destroyers escorting them.

[4] On 7 March 1943, she picked up the commanding officer of the collier Nojima Maru and 44 infantrymen from lifeboats off the northern coast of New Guinea south of Dampier Strait.

[4] Ro-101 called briefly at Rabaul on 8 March 1943 to discharge the survivors, then put back to sea the same day to come to the assistance of Ro-103, which had run aground on a reef off Kiriwina in the Trobriand Islands.

[4] She again got underway from Rabaul on 19 March 1943 to conduct a war patrol southeast of Guadalcanal, but she soon had to return when most of her crew fell ill with food poisoning.

[4] While en route, she was off Cape St. George on New Ireland at 03:40 on 21 May 1943 when she sighted a four-engine bomber — probably the United States Army Air Forces B-17E Flying Fortress Honi Kuu Okole (Hawaiian for "Kiss My Heart"), which was operating from Dobodura Airfield on New Guinea that night when a Japanese Nakajima J1N1 (Allied reporting name "Irving") night fighter shot it down[4] — crashing in flames and observed two parachutes from the plane.

[4] She was ordered to approach from west of Rendova and attack ships off the U.S. landing area at Munda, but she was unable to penetrate the PT boat screen protecting the beachhead.

[4] On 8 July 1943, Ro-101 began her sixth war patrol, ordered to return to the central Solomon Islands and attack ships in Kula Gulf off the U.S. beachhead at Rice Anchorage on the northern coast of New Georgia.

[4] While she was on the surface recharging her batteries in Kula Gulf on 12 July 1943 at approximately 08°00′S 157°19′E / 8.000°S 157.317°E / -8.000; 157.317, the U.S. Navy destroyer USS Taylor, escorting a convoy, detected her on radar at 16:50.

[4] She remained submerged for two hours after Taylor's depth-charge attack, and her interior temperature rose to 104 °F (40 °C) before she surfaced toward evening.

[4] After sunset, Ro-101's crew observed searchlights and heard heavy gunfire to seaward as U.S. and Japanese warships fought the Battle of Kolombangara.

[4] She headed for Rabaul, and while she was on the surface recharging her batteries west of Shortland Island on the afternoon of 13 July 1943, an Allied patrol plane attacked, dropping two bombs as she crash-dived and knocking out her remaining periscope.

[4] After completion of her repairs, Ro-101 got underway from Rabaul on 7 August 1943 to begin her seventh war patrol, ordered to return to the Kolombangara area.

[4] At around 01:00 on 18 August 1943, her commanding officer observed the flashes of gunfire to the north through her periscope as U.S. and Japanese destroyers fought the Battle off Horaniu.

[4] Saufley's crew then heard a large underwater explosion, and by 17:35 a slick of diesel oil covered a 1-square-nautical-mile (3.4 km2; 1.3 sq mi) area of the ocean's surface centered around 10°57′S 163°56′E / 10.950°S 163.933°E / -10.950; 163.933 (Ro-101).