After shakedown out of Bermuda and tests en route to Argentina, the new destroyer departed New York on 10 November 1944, escorting the battleships Missouri, Texas, Arkansas and aircraft carriers Shamrock Bay and Wake Island to the Pacific.

She transited the Panama Canal and touched San Francisco, Pearl Harbor, and Eniwetok before joining the 3rd Fleet at Ulithi 27 December.

On 9 January, as General Douglas MacArthur's troops landed on the beaches at Lingayen, planes from McCain's carriers hit Japanese airstrips on Formosa and the Pescadores to neutralize air opposition to the Luzon invasion.

That night McCain's ships slipped through Luzon Strait into the South China Sea where they could be on call to support the Allied beachheads while striking strategic enemy positions along the southeastern coast of Asia and searching for the Imperial Fleet.

In the next 10 days, they lashed out at Hong Kong, Hainan, and the Indochinese coast causing much damage ashore and sinking 44 ships totaling 132,700 tons.

At the end of this sweep into enemy waters Admiral William Halsey reported, "the outer defenses of the Japanese Empire no longer include Burma and the Netherlands East Indies; those countries are now isolated outposts, and their products are no longer available to the Japanese war machine..." John W. Weeks returned with her carriers to Ulithi on 28 January.

After inflicting considerable damage to Japanese air power, John W. Weeks steamed toward Iwo Jima to give direct support to Marines fighting for the island.

For the remainder of the war, John W. Weeks participated in the final assault on the Empire Islands, engaging in radar picket duty, shore bombardment, rescue missions and the antishipping sweep off Tokyo Bay.

During this cruise she escorted the royal yacht HMY Britannia, with Queen Elizabeth II of the United Kingdom aboard, from Chicago to Sault Ste.

When this display of national strength and determination forced the Kremlin to withdraw the missiles, John W. Weeks returned via San Juan, Puerto Rico, to Norfolk.

On New Year's Day, en route to the Red Sea to join that U.S. Middle East Force, she was the first ship to transit the Suez Canal during 1964.

She headed west from Karachi on 6 February; refueled at Aden; then turned south for patrol along the Zanzibar coast during the revolution there, and off Kenya and Tanganyika during unrest in those countries.

After overhaul in Norfolk Naval Shipyard, the destroyer departed Hampton Roads on 9 November for Guantanamo Bay and refresher training.

After serving as sonar school ship at Key West during March and April, the veteran destroyer departed Norfolk 16 May for European waters.

During the remainder of the year she served as school ship at Key West and joined in ASW exercises along the Atlantic Coast and in the Caribbean.

Steaming via San Juan, Puerto Rico, and Recife, Brazil, she touched at African ports on the east and west coasts of that continent and ranged Africa from the Gulf of Guinea to the Red Sea.