The second U.S. Navy ship named Herndon (DD-638) was launched on 2 February and commissioned on 20 December 1942. The Herndon began war duties escorting a convoy from New York to Casablanca early in 1943. The Herndon also took part in the Sicilian Campaign, and during July 1943 she operated in the antisubmarine and fire-support missions, assisting troops in Southern Europe.
After departing the Mediterranean area of operations in August 1943, the Herndon again escorted troops and material, this time from the United States to Britain in preparation for the invasions at Normandy. Providing gunfire support during the 6 June 1944 D-Day operations, the Herndon operated ahead of the first assault waves, assisting with the indispensable bombardment of enemy positions around Omaha Beach. The Herndon was a part of the joint task force screening carriers when the invasion of Southern France began in August 1944.
For much of the remainder of 1944, the Herndon took part in convoy escort duties in the Mediterranean and along the Atlantic coast, and in February 1945, she escorted Franklin D. Roosevelt on the first leg of his trip to Yalta. In April 1945, the Herndon set sail for the Pacific to join the fight against the Japanese; she arrived at Pearl Harbor on 15 May 1945. From 12 July until the surrender of Japan in August 1945, she escorted convoys among Eniwetok, Guam, and Saipan.
Following the end of World War II, the Herndon sailed for China. On 16 September 1945, Vice Admiral Kanako, Imperial Japanese Navy, and his staff came aboard to sign the unconditional surrender of all Japanese-controlled military and merchant vessels in the Tsingtao area. Until December, the Herndon patrolled along the Korean and Chinese coasts, aided in the repatriation of Japanese troops, and assisted with the movement of Chinese Nationalist forces.
In early December 1945, the Herndon participated in Operation Magic Carpet, assisting with the transfer of U.S. veterans to the U.S. mainland. The Herndon was decommissioned on 8 May 1946. She was moved to Philadelphia in 1947 but was not stricken from the Navy list until 1 July 1971. She was sunk as a target on 23 May 1972.