Naval Detachment in Turkish Waters to protect American interests as the Near East was in turmoil with civil strife in Russia, and Greece at war with Turkey.

She made repeated visits to ports in Turkey, Bulgaria, Russia, Greece, Egypt, Mandate Palestine, the Syrian Federation, Tunisia, Dalmatia, and Italy, and kept up gunnery and torpedo practice with her sisters until her return to Boston, Massachusetts, for an overhaul on 26 July 1924.

When the Japanese attacked Pearl Harbor on 7 December 1941, Edsall was en route to Batavia (now Jakarta) with her sister ships when word was received.

Edsall intercepted a Japanese fishing trawler, Kofuku Maru (later renamed MV Krait and used extensively by Australian special forces) with four small boats in tow and escorted them into Singapore before turning them over to HMAS Goulburn.

Edsall and her division joined the heavy cruiser USS Houston and other US units at Surabaya on 15 December 1941 and escorted shipping retiring to the relative safety of Darwin, Australia.

After fueling operations in the Lesser Sunda Islands, Edsall and Alden were escorting the Darwin-bound oiler USS Trinity in the Beagle Gulf 40 nautical miles (74 km; 46 mi) west of Darwin.

Continuing to escort convoys in northern Australian waters, Edsall was damaged when one of her own depth charges exploded during an anti-submarine attack on 23 January 1942 in the shallow — 8-fathom (48 ft; 15 m) — Howard Channel.

On 28 February, the two destroyers rendezvoused with the oiler USS Pecos off Flying Fish Cove, Christmas Island some 250 miles (400 km) southwest of Tjilatjap.

They headed directly south into the Indian Ocean for the rest of 28 February in high winds and heavy seas; between 0430 (USN/local time) and 0815 on 1 March all Langley's crew were transferred to Pecos.

Fifteen minutes later the battleships of Vice Admiral Gunichi Mikawa's Sentai 3/1 (Hiei and Kirishima) opened fire with their main battery of 14-inch (356 mm) guns at extreme range (30,000 yards, 27,000 m).

All shots missed as the destroyer conducted evasive maneuvers that ranged from flank speed, about 26 knots (48 km/h; 30 mph), to full stop, with radical turns and intermittent smoke-screens.

The skill shown by Edsall in dodging extensive shelling during an extended engagement reportedly led some of the Japanese naval personnel involved to refer to the American vessel as "the dancing mouse".

Vice Admiral Nagumo ordered airstrikes: 26 Type 99 dive bombers (Aichi D3A) (kanbaku) in three groups (chutai) took off from the carriers Kaga (8), Hiryū (9), and Sōryū (9).

Finally, at 17:31 hrs (19:01 IJN/Tokyo time) Edsall rolled onto her side, "showing her red bottom" according to an officer aboard the Hiei, and sank amid clouds of steam and smoke in 18,000 feet (5,500 m) of water some 200 miles (320 km) east of Christmas Island.

Japanese Imperial Navy officers aboard the cruiser Chikuma several years later reported that a number of men may have survived the sinking of Edsall as they were found in the water on liferafts, cutters or clinging to debris.

However, due to a submarine alert, the Japanese only stopped long enough to rescue a handful before they received orders to retire, leaving the others to perish in the Indian Ocean.

War crimes trials conducted in 1946–1948 concerning other murders that occurred in or near Kendari by IJN personnel recorded fragmentary information about the killings of Edsall survivors, but were not recognized as such by Allied investigators, and were not pursued.

L. Ron Hubbard claimed that he had served on Edsall during World War II and that, following her sinking, he swam to shore and remained in the jungle as the ship's sole survivor.