With the start of the Pacific War on 7 December 1941, Nowaki steamed with the fleet to support the invasion of the Philippines, and it was the next day she scored her first victory on an enemy ship.

The Norwegian cargo ship Helius was located by the 4th destroyer division, prompting Nowaki and Hagikaze to inspect her, and ordered Helius to regroup with the fleet, capturing the vessel, escorting her to Japanese waters where she was renamed the Setsuzan Maru and transferred to the Imperial Japanese Army.

[4][5] On 1–4 March, while in company with the cruisers Maya, Atago, Takao, and destroyer Arashi, she was involved in sinking a number of Allied vessels during operations in the Java Sea.

On 4 March, Nowaki assisted in sinking the Australian sloop Yarra and the British Motor Minesweeper 51, tanker Francol, and depot ship Anking.

Nowaki fled Truk on 17 February 1944 in the midst of the massive American air and surface attack known as Operation Hailstone and escaped pursuit by US Task Force 50.9 with minor splinter damage despite being straddled several times by 16 inch salvos from USS Iowa and USS New Jersey at extreme range.

In the Battle off Samar on 25 October 1944, Nowaki took part in the torpedo attack on the U.S. escort carriers and assisted in sinking the destroyer USS Johnston.

[6] Lit aflame and badly crippled by gunfire, Nowaki was finished off by torpedoes from the destroyer USS Owen, 65 miles (105 km) east-southeast of Legaspi (13°0′N 124°54′E / 13.000°N 124.900°E / 13.000; 124.900).