At the outbreak of the war, Smith was in San Francisco, California, where she was attached to Destroyer Squadron (DesRon) 5, performing escort duty between the west coast and Pearl Harbor until April 1942.

On 7 April, Smith was assigned to Task Force (TF) 1, composed of Battleship Division 3, which held extensive training exercises along the West Coast until departing for Pearl Harbor on 1 June.

Smith was then assigned to TF 17, commanded by Vice Admiral Marc Mitscher, engaged in war patrols and training exercises for a month; then escorted a convoy back to San Francisco.

After overhaul and subsequent sea trials in the area, she returned to Pearl Harbor in mid-August and began a period of training and upkeep.

TF 16 departed Pearl Harbor on war patrol, on 16 October, and was joined the following week by the cruisers Portland and San Juan with their destroyer screen.

[1] With 57 killed or missing, 12 wounded, her magazines flooded, and temporary loss of steering control from the pilothouse, Smith retained her position in the screen with all serviceable guns firing.

The destroyer Gridley joined the screen there, and the ships proceeded to Guadalcanal where Smith performed antisubmarine patrols until 12 March.

She then returned to Espiritu Santo and participated in various patrols and tactical and logistical exercises with TF 10 in the New Caledonia-Coral Sea area until 28 April.

Smith was attached to DesRon 5 which conducted exercises in the Townsville-Cape Moreton area to 10 June, and then escorted merchant shipping and landing craft to Milne Bay, remaining there the remainder of July.

The squadron returned to Milne Bay and participated in exercises until 2 September when it sailed with TF 76 for the Huon Gulf area of New Guinea.

Smith bombarded targets in her assigned area of "Red Beach" prior to landings by the 9th Australian Infantry Division on 4 September.

The task force suffered enemy air attacks, but these did not manage to damage it and they lost 16 planes to fighter cover or naval gunfire.

Smith stood out from Buna on Christmas Day as escort for the Cape Gloucester Attack Force (TF 76) and as a unit of the bombardment group.

On 17 March, Smith, with DesRon 5, departed the South Pacific en route to San Francisco via Pearl Harbor.

The overhaul period there was completed by 21 June; and the squadron sailed for Pearl Harbor, spending the next five weeks in training exercises and gunnery practice.

On 1 August, Smith was ordered to Eniwetok and patrolled the enemy-occupied Marshall Islands until 24 September when she joined TG 57.9, composed of Cruiser Division 5, and departed for Saipan.

The task group began offensive patrols of the Northern Marianas to protect that Central Pacific outpost from enemy attack.

She was ordered to rendezvous on 6 December with the Ormac Attack Group to bombard enemy positions ashore and then to land the 77th Army Division there.

The group arrived in the Ormac Bay area the next morning, and Smith was stationed northeast of Ponson Island as fighter director ship.

Smith and DesRon 5, departing San Pedro with a resupply echelon for Ormac Bay on 11 December, were attacked that evening in Leyte Gulf by a force of enemy planes.

No other hits were sustained by the destroyers, and Smith continued resupply operations until 17 December when she sailed to Manus for logistics and maintenance.

En route to Mindoro on 24 February, Smith picked up a radar contact that failed to respond to her blinker requesting identification.

The group sortied from Morotai on 27 April 1945, transporting the 26th Australian Infantry Brigade to Tarakan Island, Borneo, for an amphibious landing.

Smith began preliminary bombardment of the landing beaches at 0700, 1 May, and remained on station until the 19th as call fire support ship, screening picket, and harbor entrance patrol.

Smith began shore bombardment at 0700, 1 July, and received return fire from enemy guns ashore that splashed close aboard.