Upon commissioning, Truxtun completed shakedown and began duty along the east coast with the Atlantic Fleet as a unit of Division 39, Destroyer Squadron 3.

She spent a total of eight out of the 13 months between September 1926 and October 1927 patrolling the Yangtze River while competing factions in China fought one another - and occasionally otherwise neutral third parties.

On 15 September, the destroyer stood out of Hampton Roads, retransited the canal, and returned to San Diego on 9 November to resume operations with the Battle Force.

In late May and early June 1940, the warship made a voyage to Casablanca in French North Africa and then resumed neutrality patrols off Florida and in the Caribbean.

Between late February and mid-March, she made two voyages to Halifax, Nova Scotia, returning to the United States at the Washington Navy Yard on both occasions.

For the remainder of her career, Truxtun patrolled the North Atlantic sea lanes and escorted convoys from New England and Canadian ports – via NS Argentia, Newfoundland – to Reykjavík, Iceland.

At 0410 on 18 February[1] while acting as escort to USS Pollux in Placentia Bay, Newfoundland, Truxtun ran aground "in a howling gale"[2] between the outport communities of Lawn and St. Lawrence, near Chambers Cove.

Under extremely violent and freezing sea conditions she broke up almost immediately after grounding and, in spite of the heroic efforts of the local populace, lost 110 members of her crew to the elements.

[3] Robert Chafe's play, Oil and Water, depicts the story of Lanier Phillips, the sole African American survivor of the sinking of Truxtun.