The Welles' task unit arrived at Funafuti in the Ellice Islands on 21 January 1944, and sailed for New Guinea the following week. On 5 February 1944, the Welles joined the 7th Fleet at Milne Bay. Her first taste of combat came on 29 February when she provided gunfire support for the U.S. Army's 1st Cavalry elements landing on Los Negros Island in the Admiralties. During these actions, the Welles came under enemy fire from several coastal positions but sustained no damage.
Throughout the spring of 1944, the Welles took part in several antisubmarine operations and supported amphibious landings at Humboldt Bay, Sarmi, and Biak Island. During early summer of 1944, she screened logistics convoys along the New Guinea coast, and also supported the capture of Noemfoor Island. In late July, she participated in the last amphibious operation in New Guinea at Cape Sansapor.
The Welles joined the 3rd Fleet at Florida Island in the Solomons, and in mid-September 1944, took part in the assault on Peleliu and Angaur. After operations at Palau, she joined Task Group 77.2 and moved into Leyte Gulf for the invasion of the Philippines. During this invasion, the Welles provided fire support, air defense, and antisurface support until she sailed to Ulithi Atoll in late 1944 to join the screen of the Fast Carrier Task Force.
After participating in the invasions at Luzon, Iwo Jima, and Okinawa, the Welles was ordered back to the United States for a major overhaul. She arrived in Bremerton, Washington, on 16 July 1945, and remained there until the cessation of hostilities.
The Welles sailed to New York through the Panama Canal on 14 October 1945, and finally stopped in Charleston, South Carolina, where she was decommissioned on 4 February 1946. The Welles was struck from the Navy list on 10 February 1968, and sold for scrap on 18 July 1969.