After shakedown in Cuban waters, Preble was assigned special duty in Mexican waters, arriving Vera Cruz 13 June. During the following weeks she made three voyages to Galveston, Texas, to obtain medical supplies including serum to fight bubonic plague which had developed during the rebellion of the Sonora triumvirate. In August she returned north to join the Atlantic Fleet in East Coast and Caribbean exercises. In January 1921 the Atlantic and Pacific Fleets joined off the Panama Canal Zone and cruised to the west coast of South America. Separating on 23 February, the Atlantic Fleet steamed back to the Caribbean.
Preble departed Newport, Rhode Island, 20 June en route to the Asiatic Station, via Suez, with units of Squadron 15. She arrived at Chefoo, China, 26 August 1922, and for the next 7 years cruised off the coast of Asia from Manchuria to Burma, in Japanese waters, and amongst the Philippines, East Indies, and Marianas Islands. In September 1923 she assisted victims of violent earthquakes which shook Japan. From 12 June to 2 July 1924 she was at Rangoon, Burma, and Calcutta, India, delivering gas and oil for a round-the-world flight of Army planes. In 1927 Preble was assigned patrol duty in strife-torn China, taking aboard American and foreign refugees and escorting merchant vessels in the Yangtze and Whangpoo Rivers. On several occasions Chinese factions fired on Preble from shore, but there were no casualties.
Preble departed Tsingtao, China, 12 July 1929 and returned to San Diego, California, 17 August 1929. For several years she was based at San Diego, cruising along the western seaboard of the United States, with operations in waters of Mexico and the Caribbean. She was assigned to Rotating Reserve Destroyer Squadron 20 at the Mare Island Navy Yard 24 September 1932. In May 1934 Preble engaged in Fleet Problem 15 off the Panama Canal and in Cuban waters, before returning to the Pacific. She participated in Fleet Problems 16 and 18 in the Hawaiian area in May-June 1935 and April-May 1937.
On 19 May 1937 Preble was transferred from Destroyers, Battle Force, to duty with Minecraft, Battle Force. Converted to a light minelayer, she was reclassified DM-20, effective 30 June 1937. She departed Pearl Harbor 20 September 1937 for mine training operations on the West Coast and returned to Hawaii in December. She remained in the Hawaiian area until the outbreak of World War II, engaging in scheduled mining exercises and fleet maneuvers.
On the night of 31 January Tracy (DM-19), Montgomery (DM-17), and Preble laid mines in the mouth of the Tenambo River, Guadalcanal, to prevent the evacuation of enemy troops. During the next two months Preble performed escort duties to the New Hebrides and Russell Islands.
On the night of 6 May Preble with minelayers Gamble (DM-15) and Breese (DM-18) in company with Radford (DD-446) laid mines in Ferguson Passage between Gizo and Wanawana Islands in the Solomons. On the night of 7-8 May these mines sank a Japanese destroyer and damaged two others which were sunk the next day by torpedo bombers from Guadalcanal.
On 24 May Preble rescued 85 survivors from torpedoed SS Stanvac Manila. On the night of 28 June Breese, Gamble, and Preble mined the waters near Shortland Island to prevent units of the Japanese fleet based there from interfering with landing operations on Rendova Island in the New Georgia Group, which were to be carried out at dawn. During July and August Preble again served as an escort vessel. On 9 September she departed Noumea for San Francisco.
After overhaul and convoy escort duty to Pearl Harbor, Preble reached Majuro, Marshall Islands, 3 February 1944 where she served as antisubmarine screen and mine layer before returning to Pearl Harbor. She then made three escort voyages from Pearl Harbor to Marshall Islands ports. After minesweeping training, Preble departed Purvis Bay, Florida Island, 6 September, with minesweeping units of Rear Admiral Jesse B. Oldendorf’s TG 32.5. Arriving off Peleliu in the early morning Of 12 September, while fire support ships opened bombardment, Preble separated to investigate the shoals between Anguar and Peleliu Islands where the enemy had been suspected of planting acoustic mines. The next day she helped rescue survivors of Perry (DMS-17) which had struck a mine. She continued to perform various screening and minesweeping duties.
Preble arrived at Manus, Admiralty Islands on 1 October, where she joined mine sweeping Task Group 77.5 which arrived off the entrance to Leyte Gulf 17 October where she remained laying buoys and acting as mine destruction vessel for 6 days before returning to Manus. After training at Manus, she returned to San Pedro Bay 1 January 1945, but steamed a month later for Pearl Harbor and much needed repairs in the States, arriving San Francisco 8 March.
Returning to Pearl Harbor 8 May, Preble was redesignated a miscellaneous auxiliary vessel (AG-99) 5 June. She was assigned to duty escorting aircraft carriers engaged in training, acting as anti-submarine patrol vessel and plane guard during flight operations. She reached Guam with Vella Gulf (CVE-111) 20 July, subsequently escorting Vella Gulf to Okinawa. After returning to Guam, she escorted Sitkoh Bay (CVE-86) to Samar, Philippines, arriving 20 September.
Preble earned 8 battle stars for World War II service.
See USS Preble for other ships of this name.