After shakedown, Maddox departed New York 2 January 1943 for Norfolk, where she commenced escort duties. Following her first two convoy missions, safeguarding fleet oilers plying between Norfolk and the petroleum centers of Galveston and Aruba, Maddox began a series of transatlantic voyages escorting convoys from New York and Norfolk to north Africa.
On 8 June 1943, Maddox departed Norfolk for Oran, Algeria, where she became a unit of TF 81, the assault force for the Sicilian invasion. As the assault troops landed 10 July, Maddox was on antisubmarine patrol about 16 miles offshore. Steaming alone, the destroyer was attacked by a German dive bomber. One of the bombs exploded Maddox’s after magazine, causing the ship to roll over and sink within two minutes.
Maddox was struck from the Navy list 19 August 1943. She earned two service stars during World War II.