Patterson departed Puget Sound Navy Yard 26 November 1937, calling at San Francisco en route to Pearl Harbor, arriving 7 December.

She arrived at San Pedro from Hawaii 28 April for operations along the western seaboard and combined fleet maneuvers that once took her through the Panama Canal and into the Caribbean Sea.

On 28 December, returning from patrol, she rescued 19 survivors of merchant ship Marimi adrift for several days after having been torpedoed by a Japanese submarine.

In the following weeks, her duties included convoy of reinforcements for the garrison on Canton Island, Phoenix Group, and hasty voyage repairs at Pearl Harbor.

She returned to Pearl Harbor 17 May and was underway five days later, en route by way of Nouméa, New Caledonia, to join Admiral Richmond K. Turner's Expeditionary Task Force preparing in Australia for the invasion of the Solomons.

[1] As Patterson fought off aerial raiders, seven enemy cruisers and a destroyer raced down the slot of water formed by the Solomon Islands Chain and stretching southward from the Japanese base at Rabaul.

Patterson’s gunners continued shooting until the enemy, flinging torpedoes, split formation, and raced northeast in a pincer movement on the northern force of three cruisers.

[3][4] Patterson next escorted troop transports from Nouméa, New Caledonia, to the New Hebrides, patrolled off Guadalcanal out of Purvis Bay, Florida, Solomon Islands.

She soon turned back to Vella Lavella Island at full speed, having received word that unloading tank landing craft there were under enemy air attack.

Both ships entered Purvis Bay for emergency repairs, thence to Espiritu Santo, New Hebrides Islands, where Patterson received a false bow.

Training with fast attack carriers in Hawaiian waters was followed by similar battle rehearsals out of Marshall Island ports in preparation for the Marianas Campaign.

The few enemy planes that managed to get past the American carrier pilots met curtains of anti-aircraft fire from Patterson and her sister ships.

After replenishment at Manus, Admiralty Islands, Patterson made a high-speed run with attack carriers to blast enemy defenses on Okinawa and the entire Kerama Retto chain.

On 20 October her carrier task group gave direct air support to troops landing at Leyte to begin the liberation of the Philippine Islands.

She joined in the pursuit of enemy fleet units fleeing the Battle for Leyte Gulf, then helped fight off the suicide attacks of Japanese kamikaze aircraft 30 October.

There, she joined the screen of an escort carrier-bombardment task group that sailed 10 December to provide heavy gunfire support and air cover for the initial landings on Mindoro Island.

For seven days the destroyer remained in the Sulu Sea, fighting off frequent suicide attacks of enemy aerial raiders that closed her carrier task group formation.

There was a brief replenishment at Palau before Patterson again sailed with escort aircraft carriers, this time to support the invasion landings at Lingayen Gulf, Luzon, Philippines.

She rescued 106 survivors of the escort carrier Bismarck Sea, sunk by enemy torpedo plane attacks off Iwo Jima 21 February.

The fighting destroyer remained off Iwo Jima with escort carriers until 10 March, then set course for Ulithi to prepare for the capture and occupation of Okinawa, the "last stepping stone" to Japan.

Patterson sailed from Ulithi the morning of 21 March, en route with a support unit of seven escort aircraft carriers that gave direct cover to troops storming ashore at Okinawa 1 April.

She put to sea from Apra Harbor 4 June, escorting battleship New Mexico as far as Leyte in the Philippines, There she joined a troop and supply reinforcement convoy bound to Kerama Retto.