Departing Philadelphia on 24 November 1921 with military and civilian passengers, as well as a senatorial party, Argonne's maiden voyage and shakedown took the ship to Port-au-Prince, Haiti; St. Thomas, Virgin Islands; Ponce, Puerto Rico; and Santo Domingo City, Dominican Republic; before she put into Hampton Roads on 22 December.

Subsequently, returning to Philadelphia for post-shakedown availability, Argonne proceeded to the Panama Canal via Charleston, South Carolina, and after a stop at Mare Island continued across the Pacific to Cavite, in the Philippines, on her first voyage to that part of the globe.

On 7 April 1922, Commander (later Fleet Admiral) Chester W. Nimitz, along with his wife and three children, embarked on board Argonne at Pearl Harbor for passage to the east coast of the United States.

Argonne participated in one of the early lifts, transporting the second Battalion, 5th Regiment – which had been encamped at Guantánamo Bay undergoing six months of training—from Guantanamo to Bluefields, Nicaragua, between 7 and 10 January 1927.

There, she disembarked the rest of the battalion on 24 January to maintain the neutral zones between that port and the capital city of Managua, before returning thence into the Caribbean to resume tending operations with SubDiv 20.

On 1 July 1927, Argonne became part of the Control Force, with which she carried out her previous duties with the Special Service Squadron, until being transferred with SubDiv 20 to the Battle Fleet, on 19 November.

Reaching Pearl Harbor on the 28th, she then based at Lahaina, and carried out tactical exercises with the fleet, ultimately returning to Mare Island for her annual overhaul on 29 June.

Over the next eleven months, Argonne provided support services at San Diego with SubDivs 11 and 20, as the ships conducted speed and endurance tests, as well as torpedo and sound exercises.

She operated with the fleet at New York, Newport, and Hampton Roads until 26 May, when she then set course for Panama and back to San Diego, arriving at the latter port on 19 June.

Reaching the Puget Sound Navy Yard on 13 March, Argonne was drydocked, received stores and equipment, fuel oil and gasoline, and ultimately sailed for Dutch Harbor on 6 April.

Argonne remained at Dutch Harbor from 1 to 18 May, contacting USS Patoka at that port for fuel oil and provisions, but also awaiting better weather in which to conduct her surveys.

Argonne, during her time in northern waters, also assisted the Bering Sea Aerological Expedition, with weather surveys and analyses necessary for radio stations of Washington and Alaska.

She subsequently provided tender services out of New London and Newport before she proceeded to Port-au-Prince to participate in the withdrawal of the 1st Marine Brigade from Haiti on 15 August 1934.

"Impressive ceremonies on shore amidst most friendly feelings displayed by the populace" accompanied the departure of the marines, whose duties as peacekeepers had been taken over by the fully Haitianized Garde d'Haiti.

Following leave and liberty at Hampton Roads and at New Orleans, Argonne joined the fleet, transited the Panama Canal, and ultimately arrived at San Pedro on 9 November 1934.

As Base Force flagship, she provided tender and repair services for minesweepers, tugs, and harbor craft, while maintaining the only major photographic laboratory for photo-triangulation of fleet gunnery exercises.

On the morning of 7 December 1941, Argonne – flagship for Rear Admiral William L. Calhoun, Commander, Base Force, Pacific Fleet – was berthed in the first repair slip at the north end of 1010 dock, with the minesweeper Tern alongside, when aircraft from six Japanese carriers struck the Pacific Fleet as it lay at Pearl Harbor, and neutralized surrounding air and military installations.

Early in the raid, Corporal Alfred Schlag, USMC, from the ship's marine detachment, manning a .50-caliber machine gun, claimed shooting down an enemy plane as it flew over 1010 dock and turned toward Ford Island.

Sailing on the 17th, Argonne put into Suva Harbor, Fiji Islands, on the 21st, to unload cargo, and then, two days later, set course for Nouméa, New Caledonia, in company with Hovey, arriving on 27 July 1942.

Halsey exercised command of the theater from Argonne until he shifted his flag ashore, the ship proving "hopelessly inadequate" for the increase in the number of people required on the staff.

After embarking men from Carrier Aircraft Service Unit (CASU) 14, Argonne sailed for the Solomons the same day (11 August), reaching Purvis Bay, off Florida Island, on the 13th.

Sailing from Purvis Bay on 1 November 1943 in company with SS Coutant and escorted by the Royal New Zealand Navy corvette HMNZS Kiwi, Argonne arrived at Tillotson Cove, Russell Islands, the same day.

The ship remained in the Russells, carrying out repair and salvage work, until 27 April 1944, when she stood put for Majuro Atoll in the Marshall Islands.

At 0850, local time, on 10 November 1944, Argonne lay moored to a buoy in berth 14, Seeadler Harbor, when the ammunition ship Mount Hood blew up, 1,100 yards (1,000 m) away.

By the time we had recovered our stance from the force of the explosion, and faced outboard, the area in the vicinity of berth 380 (where Mount Hood had lain moored) was completely shrouded in a pall of dense black smoke.

Argonne suffered casualties as well as the destruction of a 12-inch (300 mm) searchlight, five transmitting antennas broken away, and steam, fresh-water and salt-water lines ruptured, as well as extensive damage from concussion.

After again repairing her own damage, the ship resumed her important service to the fleet, and remained in the Palaus until she sailed for the Philippines on 11 February 1945 to take up support operations for the Okinawa campaign, basing on Leyte.

Argonne remained in the western Pacific through the end of hostilities with Japan in August 1945, and briefly served with the occupation forces in Japanese waters before returning to the United States.