From 1938, the cruiser was based in Taiwan, and helped cover the landings of Japanese troops in southern China.

A Japanese-sponsored "Conference for the Cessation of Hostilities" was held at Saigon and preliminary documents for a cease-fire between the governments of General Philippe Pétain's Vichy France and the Kingdom of Siam were signed aboard Natori on January 31, 1941.

At the time of the attack on Pearl Harbor, Natori was escorting six transports carrying elements of the IJA's 48th Infantry Division from Mako, Pescadores to Aparri, northern Luzon.

The landing force was attacked by three USAAF B-17 Flying Fortress bombers of the 14th Squadron on 10 December 1941, which damaged Natori and the escorting destroyer Harukaze with near misses.

Natori was later assigned escort duties to cover the invasion force for the Dutch East Indies, and participated in the Battle of Sunda Strait on 28 February 1942.

Perth, low on ammunition, was making 28 knots (52 km/h) when the first torpedo hit her forward engine room.

At Christmas Island on 1 April 1942 the submarine USS Seawolf fired three torpedoes at Natori, but all missed.

On 21 December 1942, Natori embarked a Special Naval Landing Force, which it disembarked at Hollandia, New Guinea.

On 9 January 1943, 18 nautical miles (33 km) southeast of Ambon, Natori was sighted by the submarine USS Tautog at about 3,000 yards (3,000 m).

Repairs and modernization were completed on 1 April 1944, and Natori was assigned as the flagship of the Central Pacific Fleet's Destroyer Squadron 3.

On 5 June 1944, Natori embarked an Imperial Japanese Army detachment from Kure to Davao, Mindanao where the cruiser disembarked the Army detachment and embarked other troops for Palau, arriving on 17 June 1944 (the day before the Battle of the Philippine Sea.

On 20 July 1944, the submarine USS Bluegill patrolling off Davao spotted Natori making 26 knots (48 km/h), but was unable to gain a favorable firing position.

Natori arrived in Palau 21 July 1944 to help evacuate 800 Japanese and Korean "comfort women" to Davao.

On 12 September 1944, almost a month after her sinking, the destroyer USS Marshall captured a lifeboat with another 44 survivors from Natori aboard.