Clemson cruised in east coast and Cuban waters until placed in reserve with 50 percent complement at Norfolk Navy Yard 13 June 1920. She lay there and later at Charleston and Boston Navy Yards until she sailed to Philadelphia Navy Yard where she was decommissioned 30 June 1922.
Reclassified AVP-17, 15 November 1939, and converted into a small aircraft tender, Clemson was recommissioned 12 July 1940. On 6 August she was again reclassified, becoming AVD-4, and on 18 August reported to Commander, Aircraft, Scouting Force, Atlantic Fleet at Norfolk. From 29 August 1940 to 28 November 1941 she tended patrol planes in the Caribbean and at the Galapagos Islands. Clemson then sailed south arriving at Recife, Brazil, 6 December. She remained on the coast of Brazil until 22 January 1942 when she returned to the Galapagos Islands. For the next year the tender shuttled between there and the Caribbean as her services were required. She returned to Norfolk, Va., 2 March 1943 and then moved to Charleston, S.C., for reconversion to a destroyer (although not reclassified DD-186 until 1 December 1943).
On 30 May 1943 she joined the pioneer American hunter-killer group built around Bogue (CVE-9). Clemson made eight patrols with the group during which it sank eight German submarines, a major contribution to victory in the Battle of the Atlantic. Clemson shared in the credit for the sinking of U-175 on 13 December in 26° 19’ N., 29° 58’ W. After an overhaul at New York early in 1944, she escorted a convoy to Casablanca and back between 25 January and 9 March. Once more Clemson underwent conversion, this time to a high speed transport at Charleston Navy Yard (reclassified APD-31, 7 March 1944).
Clearing Charleston 1 May 1944 the transport reached Pearl Harbor 24 May and embarked Underwater Demolition Team 6. She then sailed westward to act as a mother ship for the UDT as it prepared beaches immediately before the invasions of Saipan, Guam, Peleliu, Leyte and Lingayen Gulf, Luzon. While entering the Gulf 5 January 1945, she drove off a Japanese air attack. Clemson escorted convoys to Ulithi, Saipan, and Okinawa before returning to San Pedro, Calif., 6 July. Re-designated DD-186, 17 July, she was still undergoing reconversion when World War II ended. She was decommissioned 12 October 1945 and sold 21 November 1946.
Clemson shared in the Presidential Unit Citation awarded the Bogue hunter-killer group, and received nine battle stars for World War II, four on her European-African-Middle Eastern campaign ribbon and five on her Asiatic-Pacific campaign ribbon.