The third Madison (DD-425) was laid down 19 September 1938 by the Boston Navy Yard; launched 20 October 1939; sponsored by Mrs. Ethel Madison Meyn, widow of Comdr. James Jonas Madison; and commissioned 6 August 1940, Lt. Comdr. T. E. Boyce in command.

 Prior to the entry of the United States into World War II, the destroyer saw over a years service opposing the spread of Axis power. In addition to neutrality patrol in the Caribbean and North Atlantic convoy duty, she was escort on two diplomatic voyages in January 1941. She escorted Tuscaloosa as the cruiser carried Adm. William D. Leahy to Portugal en route to France to become Ambassador to Vichy France Government, where he was a reminder of both the neutrality and the power of the United States. In August, she and Mayo(DD422) escorted Augusta carrying President Franklin Roosevelt to Argentia Bay, she rendezvoused with HMS Prince of Wales, carrying Prime Minister Winston Churchill.

 Following the formulation of the Atlantic Charter, Madison returned to convoy and patrol duty. She operated in the North Atlantic and along the east coast until the spring of 1942. On 4 April Madison put into Scapa Flow and became a unit of the British Home Fleet. Steaming at first between Greenock and the Mediterranean, Madison was with Wasp when that carrier delivered desperately needed Spitfires to the besieged island of Malta. These planes enabled the residents to hold on to their position as an irritant to the Axis, preventing enemy air supremacy in the western Mediterranean, and providing a future logistics base for the Allies. Returning from this mission, Madison patrolled the North Sea and the convoy routes to Murmansk.

 Resuming operations as part of the Atlantic Fleet, Madison took up her convoy duty anew. She made quick trips to Panama, the gulf ports and various ports in the United Kingdom. On 2 November she departed New York for Casablanca with a convoy of troops and supplies to support the initial invasion of north Africa. Arriving in mid-November, she remained on local patrol and escort duty off Casablanca until the end of the year.

Standing out of New York 30 January 1943, the destroyer made one convoy run to Londonderry before commencing, in february, "oil runs" from Curaco to the United Kingdom. For the remainder of the year, she continued to escort convoys of tankers and other types of merchant ships between the Netherlands West Indies, New York, north Africa, and various United Kingdom and Mediterranean ports.

Madison's next assignment was to the Mediterranean. Arriving at Oran, Algeria, 30 January 1944, she practiced shore bombardment before departing for Italy 11 February. Operating off of Anzio, she continued antisubmarine patroles and provided antiaircraft protection and support gunfire until mid-April when she commenced convoy and patrol duty throughout the Mediterranean. In August, Madison once again joined the support force for an invasion, this time in the south of France.

During operation "Anvil", Madison, on antisubmarine patrol and fire support duty, became the champion human torpedo shooter, obtaining in 1 day alone, 10 September, four certain kills and one probable.

 Returning home in January 1945, Madison escorted one more convoy to Mediterranean ports and returned before departing the east coast 21 April for the Pacific, Arriving Guam 1 July. Following a convoy run to Okinawa and back, Madison was assigned to a picket station off Ulithi. On 2 August, she raced to the site of the loss of Indianapolis to search for survivors. Later she steamed to Tokyo Bay to witness the formal surrender of the Japanese forces.

 Following the war's end, Madison remained with the occupation forces until 5 November when she sailed for Charleston S.C. Having steamed more than 300,000 miles during the course of the war, Madison arrived at Charleston 7 December 1945. She was placed out of commission in reserve 13 March 1946 at Charleston and later moved to Orange Tex. She was struck from the Navy List 1 June 1968.

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