After completing her shakedown cruise and post shakedown availability, Strong sailed on 15 October with a convoy to San Juan, Puerto Rico, and returned to Norfolk, VA, on the 27th.

She departed there two days later for New York. On 13 November, Strong sailed with convoy UGS-2 bound for North African ports. She arrived at Casablanca on 29 November and returned to New York with convoy GUF-2. Following a yard availability period, 11 to 26 December, the destroyer moved to Norfolk.

Strong sailed on 27 December 1942; transited the Panama Canal; refueled at Bora Bora, Society Islands; and arrived at Nouméa on 27 January. Strong then escorted the convoy northwest for two days and was relieved to return to Nouméa. On 1 February, she and Cony (DD 508) escorted a convoy bound for Espiritu Santo, New Hebrides. She sailed from there on 5 February for the Solomon Islands and patrolled off Guadalcanal until the 13th when she joined TF 67 composed of four cruisers and their destroyer screen.

The task force devoted most of the next month to patrol duty in waters in and around the Solomons. On 14 March, Strong, Nicholas (DD 449), Radford (DD 446), and Taylor (DD 468) were detached to bombard shore installations on Kolombangara Island and shelled targets on Vila Stanmore Plantation on 16 March. The force then resumed patrol duties in the Solomons. On the morning of 5 April, Strong made a surface radar contact at a range of 9,350 yards. The target was illuminated by her searchlight and proved to be a Japanese submarine. Strong and O'Bannon (DD 450) opened fire with all guns. Strong made at least three 5-inch hits on the submarine, and O'Bannon also scored. The submarine, RO-34, settled by the stern and went under. Depth charge patterns from the destroyers insured that it stayed down.

Strong, with TF 18, accompanied three destroyer minelayers to Blackett Strait, between Kolombangara and Arundel Island, and mined it in the early morning hours of 7 May. The next morning, four Japanese destroyers sailed around Kolombangara into the strait and the minefield. One sank immediately, two were damaged and sunk by aircraft that afternoon; and the fourth, although badly damaged, managed to escape.

On the night of 12 and 13 May, Strong and the task force bombarded Kolombangara, Enogai Inlet, and Rice Anchorage. The destroyer then began escort and patrol duty off Guadalcanal. On the afternoon of 16 June, she was about half-way between Guadalcanal and Tulagi when a flight of approximately 15 Japanese dive bombers attacked American shipping. Strong was the closest ship to the bombers as they approached in a shallow glide from the direction of Koli Point. Between 1414 and 1421, she splashed three of them.

On the morning of 5 July, American forces landed at Rice Anchorage. Strong and TF 18 were to support the landings by shelling Vila-Stanmore, Enogai, and Bairoko. Strong and Nicholas entered Bairoko Harbor to search ahead of the main force and shelled the harbor from 0030 to 0040. Nine minutes later, Strong's gunnery officer sighted a torpedo wake. Before he had time to notify the bridge, the torpedo hit her port side aft. Chevalier (DD 451) intentionally rammed Strong's bow to enable her to throw nets and lines to the stricken ship, and removed 241 men in about seven minutes. Japanese gunners on Enogai beach spotted the ships, illuminated them with star shells, and then opened fire with high explosives. O'Bannon began counter-battery fire in an effort to silence the enemy guns which were soon hitting Strong. Chevalier had to cease rescue operations lest she also get hit. Strong began to settle rapidly with a 40° to 60° list to starboard. She broke in half just before sinking. Several of her depth charges exploded, causing further injuries and loss of life. Forty-six men perished with the ship. Her name was struck from the Navy list on 15 July 1943.

Strong received two battle stars for World War II service.

Source: Naval History & Heritage Command including Dictionary of American Naval Fighting Ships.