On 23 June, she steamed westwards from Norfolk, Virginia, for the Pacific via the Panama Canal, arriving at San Pedro, California, on 16 July for two years of operations.

With the bombing of Pearl Harbor, Nashville steamed to Casco Bay, Maine, where she joined with a troop and cargo convoy to escort them to Iceland.

From June–November, Nashville patrolled the North Pacific Ocean, and participated in the attack on Kiska on 7 August, in which heavy damage was inflicted on Japanese shore installations.

After escorting troopships to Guadalcanal, Nashville, Helena, and St. Louis inflicted heavy damage on the Japanese air base at Munda on the night of 4 January 1943.

On 27 May, the light cruiser was a member of the assault force shelling Biak, Schouten Islands, where on 4 June, she sustained moderate damage from a near miss while repelling a Japanese air attack.

[4] After repairs at Espiritu Santo, New Hebrides, Nashville twice more carried General MacArthur and his staff to the invasion of Morotai, Dutch East Indies in mid-September.

Returning to Manus Island for brief repairs, Nashville left the Admiralties on 28 November as the flagship for the Commander, Visayan Attack Force, en route to the invasion of Mindoro.

[4] The Attack Group Commander, Rear Admiral Arthur Dewey Struble, shifted his flag to Dashiell, and Nashville steamed via San Pedro Bay in the Philippines and Pearl Harbor, Oahu, to the Puget Sound Naval Shipyard, arriving on 12 January 1945, for heavy repairs.

The closing months of the war were spent providing fire support for the landings at Brunei Bay, Borneo, and protecting aircraft carriers in the Makassar Straits, Dutch East Indies.

[4] Nashville, with Commander TF 73 (CTF 73) embarked, entered Shanghai harbor on 19 September 1945, to resume Yangtze River Patrol.

CTF 73 hauled down his flag on 17 November, and Nashville sailed for the US West Coast with 450 returning soldiers, as part of Operation Magic Carpet.

Nearing the US West Coast on 3 January 1946, Nashville came to the aid of St. Mary's, laboring in heavy seas with engine breakdowns and 1,800 men aboard.