At the outbreak of the war, Smith was in San Francisco attached to Destroyer Squadron (DesRon) 5 and from then until April 1942, she performed escort duty from the west coast to Pearl Harbor. 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 it departed for Pearl Harbor on 1 June. Upon her arrival, Smith was assigned to TF 17 commanded by Vice Admiral Marc Mitscher. She engaged in war patrols and training exercises for a month and then escorted a convoy back to San Francisco. After overhaul and subsequent sea trials in the Bay Area, she returned to Pearl Harbor in mid august and began a period of training and upkeep. On 15 October, she was assigned to TF 16 composed of Enterprise (CV-6) and South Dakota (BB-57). TF 16 departed Pearl Harbor on war patrol, on 16 October, and was joined the following week by Portland (CA-33) and San Juan (CL-54) with their destroyer screen.
The task force was operating northwest of the New Hebrides Islands when, on 24 October, it was notified that a Japanese carrier force was converging on Guadalcanal. TF 17 Hornet (CV-8) and its cruiser-destroyer screen, joined TF 16 and the merged force was designated TF 61.
On 26 October, scout planes from Enterprise located the Japanese force and they also found ours. At 0944, the first enemy planes were sighted and Hornet was hit by bombs 30 minutes later. At 1125, Smith was attacked by a formation of 20 torpedo planes. Twenty minutes later, a Japanese torpedo plane crashed into her forecastle, causing a heavy explosion. The forward part of the ship was enveloped in a sheet of smoke and flame from bursting gasoline tanks and the bridge had to be abandoned. The entire forward deck house was aflame, making topside forward of number one stack untenable. Smith's gunners splashed six of the planes. By early afternoon, the crew had extinguished all of the fires forward. With 57 killed or missing, 12 wounded, her magazines flooded, and temporary loss of steering control from the pilot house, Smith retained her position in the screen with all serviceable guns firing. Action was broken off in the evening, and Smith headed to Nouméa for temporary repairs. She was patched up and underway for Pearl Harbor on 5 November. At Pearl Harbor, she underwent a yard overhaul and sea trials that lasted into February 1943.
Smith departed on 12 February for Espiritu Santo as screen for Wright (CVL-49). Gridley (DD-380) 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 returned to Pearl Harbor the following month for logistics and then sailed for Australia.
Smith was attached to DesRon 5 which conducted exercises in the Townsville Cape Moreton area to June 10th, and then escorted merchant shipping and landing craft to Milne Bay, remaining there the remainder of July. Smith departed for McKay, Australia, and yard availability on 1 August. When this was completed, she returned to Milne Bay for further exercises and preparations for impending operations with the Seventh Fleet.
Smith, with destroyers Perkins (DD-377), Conyngham (DD-371), and Mahan (DD-364), bombarded Finschhafen, New Guinea, on 23 August without opposition. 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. She remained in the area on offensive sweeps antisubmarine patrols, and as antiaircraft defense until 18 September. On the night of 7–8 September, the squadron shelled Lae.
During the period 20 to 23 September, Smith participated in the bombardment and landings at Finschhafen as a unit o£ TF 76. Enemy air attacks were carried out against the task force with no damage to it, but they lost 16 planes to fighter cover or naval gunfire. Smith then returned to Holuicote Bay for resupply operations to Lae and Finschhafen.
On 3 October, Smith, Henley (DD-391), and Reid (DD-369) were assigned to make an antisubmarine sweep of Huon Gulf. At 1821, three torpedo wakes were sighted abaft Smith's port beam. She made a right full rudder and slipped between two of the torpedoes one passing 500 yards to port, the other 200 yards to starboard. Henley took a torpedo on the port side and, six minutes later, broke in half, disappearing from sight at 1832. Smith made a depth charge attack that proved futile. The squadron spent the remainder of the month in resupply operations to forward areas. Smith had a short availability period in Milne Bay the first of November and then returned to the Lae–Finschhafen area.
On 14 December, Smith was attached to the Arawe Attack Force forming at Holnicote Bay and departed for that operation. The next morning, she shelled "Orange Beach," Cape Merkus, and covered the operation with other units of DesRon 5. The squadron then returned to Milne Bay to prepare for the invasion of Cape Gloucester, New Britain.
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. The next morning, she shelled "Green Beach," Cape Gloucester in preparation for the assault by marines of the First Marine Division. She escorted resupply ships to the landing area the following week.
Smith was a unit of the Saidor Attack Force when, on 1 January 1944, she was rammed astern by Hutchins (DD-476) and forced to return to Milne Bay for repairs. She soon rejoined the squadron in resupply operations to Cape Gloucester and the Lae area. Smith shelled enemy gun emplacements in the vicinity of Herwath Point and Singor, on 13 February, in preparation for the landings there.
On the 28th, Smith departed Cape Sudest, as a unit of the Admiralty Islands Attack Group, with 71 officers and men of the First Cavalry Division aboard to be landed on Los Negros Island. The next morning, she began bombardment of designated targets along the northern shore of Hyane Harbor. The troops were landed and Smith provided call fire until that evening when she shuttled more troops to the landing area.
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 Marshalls until 24 September when she joined TG 57.9, composed of Cruiser Division 6, and departed for Saipan. The task group began offensive patrols of the Northern Marianas to protect that Central Pacific outpost from enemy attack. Smith returned to Eniwetok in early October, made an escort trip to Ulithi, and then sailed to Hollandia.
Smith was attached to the Seventh Fleet on 26 October and the next day set course for Leyte Gulf, P.I., arriving at San Pedro three days later. She patrolled Leyte Gulf as a unit of TG 77.1 from 1 to 16 November and then escorted a convoy to New Georgia and back. She was ordered to rendezvous on 6 December with the Ormoc Attack Group to bombard enemy positions ashore and then to land the 77th Army Division there. The group arrived in the Ormoc Bay area the next morning, and Smith was stationed northeast of Ponson Island as fighter director ship. At 0945, enemy aircraft attacked the fleet. At least three suicide planes dived on Mahan and three on Ward (APD-16). Both were badly damaged and later sunk by friendly gunfire when it was ascertained the fires could not be brought under control or the ships salvaged. Air attacks continued throughout the morning and when the landing force was disembarked the attack group retired to Leyte.
Smith and DesRon 5, departing San Pedro with a resupply echelon for Ormoc Bay on 11 December, were attacked that evening in Leyte Gulf by a force of enemy planes. At 1704, Reid was hit by a bomb and a suicide plane. There was a violent explosion, and she heeled over and sank at 1706. Smith splashed four of the enemy planes. The next morning, the formation was again attacked by Japanese planes, and Caldwell (DD-605) was hit by a kamikaze which set her afire. No other hits were sustained by the destroyers, and Smith continued resupply operations until the 17th when she sailed to Manus for logistics and maintenance.
Smith was back in Leyte Gulf on 6 January 1945 as a unit in the screen of TG 79.2 proceeding to support amphibious landings in Lingayen Gulf, Luzon. There was a heavy air attack two days later in which Kitkun Bay (CVE-71) was seriously damaged by a kamikaze. Smith, 3,000 yards away, stood by to rescue survivors. She took on board over 200 sailors. On 9 January, she was able to transfer these men back to Kitkun Bay which was now proceeding under her own steam. Smith was then assigned to patrol the northern Lingayen Gulf. From 28 January to 20 February, she screened convoys to Hollandia, Sansapor, and Leyte. In Leyte on the 20th, she was assigned to screen a convoy to Mangarin Bay, Mindoro. While passing through the Mindanao Sea the next morning, Renshaw (DD-499) was hit by a torpedo and seriously damaged. Smith went alongside to transfer wounded, furnish electricity, and begin pumping out the after engine room with fire and bilge pumps. She towed Renshaw for six hours until she was relieved, to proceed independently to San Pedro and transfer the wounded who had been taken on board.
En route to Mindoro on the 24th, Smith picked up a radar contact that failed to respond to her blinker requesting identification. When the contact was illuminated, it proved to be a Japanese steam lugger of 200 tons. The target was taken under fire at 2147 and destroyed by 2158. Smith departed Mindoro on 26 February as a unit of the Puerta Princesa, Palawan Attack Group (TG 78.2). She was on station two days later and at 0818 began firing preliminary shore bombardment on "White Beach." She then patrolled the entrance of Palawan Harbor until 4 March. Smith was relieved from patrol and made two runs to Palawan as escort for supply ships.
On 24 March, Smith again sailed with TG 78.2. This time the objective was to transport and land the Americal Infantry Division at Cebu City, Cebu Island. Smith bombarded the landing beaches the morning of the assault, 28 March, and after the forces landed, provided them with call fire. Over one eight-day period, she expended 1,200 rounds of 5-inch ammunition. On 23 April, she departed the Philippines with orders to join TG 78.1 at Morotai.
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 retired to Morotai, sailed to Zamboanga, rendezvoused with Mettawee (AOG-17) and escorted her back to Tarakan. She then provided night gunfire support for the Australians until ordered back to Morotai.
There, she was attached to Rear Admiral Noble's TG 78.2 on 26 June and again sailed for Borneo. This time the objective was Balikpapan, Borneo, where the First Australian Corps was to be landed. Smith began shore bombardment at 0700, 1 July, and received return fire from enemy guns ashore that splashed close aboard. The Japanese gunners finally got her range and sent three shells through her number one stack. The shells failed to explode, and only superficial damage was done. One visible gun emplacement was taken under counterbattery fire and silenced. Smith left the next day for Morotai, picked up a resupply convoy, and was back in Balikpapan on 16 July. She departed on the 24th for San Pedro and tender availability.
Smith departed the Philippines on 15 August for Buckner Bay; remained there for two weeks and sailed for Nagasaki Harbor, Kyushu. On 15 September, 90 ex-prisoners of war boarded; and, the next morning, Smith steamed for Okinawa to transfer them to the United States. She picked up 90 more Allied military personnel at Nagasaki on 21 September and transported them back to Renville (APA-227) in Buckner Bay.
Smith arrived in Sasebo on 28 September and departed two days later for San Diego, via Pearl Harbor. She docked in San Diego on 19 November and remained there until ordered to Pearl Harbor on 28 December for disposal or inactivation. She arrived in Pearl Harbor on 3 January 1946 and assumed an inactive status. Smith was decommissioned on 28 June 1946 and struck from the Navy list on 25 February 1947.
Smith received six battle stars for World War II service.