At the time of the attack on Pearl Harbor on 7 December 1941, Nagatsuki was assigned to Destroyer Division 22 under Destroyer Squadron 5 of the 3rd Fleet.
She sortied from the Mako Guard District in the Pescadores as part of the Japanese invasion force for Operation M (the invasion of the Philippines), during which time the destroyer helped screen landings of Japanese forces at Lingayen Gulf and at Aparri.
While at Lingayen Gulf, Nagatsuki suffered light damage due to strafing attacks by USAAF aircraft, which left one crewman dead and five injured.

In early 1942, Nagatsuki was assigned to escorting troop convoys from French Indochina for Operation J (the invasion of Java, Netherlands East Indies), From 10 March 1942 Nagatsuki and Destroyer Division 5 were reassigned to the Southwest Area Fleet and escorted troop convoy from Singapore to Penang, and Rangoon.
The destroyer returned to Sasebo Naval Arsenal for repairs on 19 September, and rejoined the fleet on 9 November, continuing escort patrol duties.

At the end of January 1943, Nagatsuki escorted the seaplane tender Kamikawa Maru from Sasebo via Truk and Rabaul to Shortlands, and remained throughout February to cover Operation KE (troop evacuations from Guadalcanal) and to escort convoys to Palau, Wewak and Rabaul.
On 25 February, Nagatsuki was reassigned to the IJN 8th Fleet.
The ship participated in several Tokyo Express troop transport missions throughout the Solomon Islands through the end of June, especially to Kolombangara and Tuluvu.
On 4–5 July, while on a run to Kolombangara, Nagatsuki engaged the US destroyer USS Strong, which she helped sink with her torpedoes.

However, the following day, during the Battle of Kula Gulf, Nagatsuki was holed by a six-inch shot.
The ship's captain, Lieutenant Commander Tameo Furukawa, grounded the vessel near Bambari Harbor 08°02′S 157°12′E on Kolombangara to land his troops; however, later, even with the assistance of sister ship Satsuki, it proved impossible to refloat the vessel, and she was attacked and destroyed the following day, 6 July, by Allied aircraft.
The crew suffered eight dead and thirteen injured, but the survivors later reached the Imperial Japanese Army base at Vila on Kolombangara on foot.
Nagatsuki was struck from the Navy List on 1 October 1943.
At the time of the attack on Pearl Harbor on 7 December 1941, Nagatsuki was assigned to Destroyer Division 22 under Destroyer Squadron 5 of the 3rd Fleet. She sortied from the Mako Guard District in the Pescadores as part of the Japanese invasion force for Operation M (the invasion of the Philippines), during which time the destroyer helped screen landings of Japanese forces at Lingayen Gulf and at Aparri. While at Lingayen Gulf, Nagatsuki suffered light damage due to strafing attacks by USAAF aircraft, which left one crewman dead and five injured.
In early 1942, Nagatsuki was assigned to escorting troop convoys from French Indochina for Operation J (the invasion of Java, Netherlands East Indies), From 10 March 1942 Nagatsuki and Destroyer Division 5 were reassigned to the Southwest Area Fleet and escorted troop convoy from Singapore to Penang, and Rangoon. The destroyer returned to Sasebo Naval Arsenal for repairs on 19 September, and rejoined the fleet on 9 November, continuing escort patrol duties.
At the end of January 1943, Nagatsuki escorted the seaplane tender Kamikawa Maru from Sasebo via Truk and Rabaul to Shortlands, and remained throughout February to cover Operation KE (troop evacuations from Guadalcanal) and to escort convoys to Palau, Wewak and Rabaul. On 25 February, Nagatsuki was reassigned to the IJN 8th Fleet. The ship participated in several Tokyo Express troop transport missions throughout the Solomon Islands through the end of June, especially to Kolombangara and Tuluvu. On 4–5 July, while on a run to Kolombangara, Nagatsuki engaged the US destroyer USS Strong, which she helped sink with her torpedoes.
However, the following day, during the Battle of Kula Gulf, Nagatsuki was holed by a six-inch shot. The ship's captain, Lieutenant Commander Tameo Furukawa, grounded the vessel near Bambari Harbor 08°02′S 157°12′E on Kolombangara to land his troops; however, later, even with the assistance of sister ship Satsuki, it proved impossible to refloat the vessel, and she was attacked and destroyed the following day, 6 July, by Allied aircraft. The crew suffered eight dead and thirteen injured, but the survivors later reached the Imperial Japanese Army base at Vila on Kolombangara on foot. Nagatsuki was struck from the Navy List on 1 October 1943.
Japanese destroyer Nagatsuki (1926)