Construction of Stethem began on 18 May 1992 with the ship's keel being laid down at the Ingalls Shipbuilding Division of Litton Industries in Pascagoula, Mississippi on 11 May 1993.

The vessel then transited the Panama Canal and was officially commissioned on 21 October 1995 at the Naval Construction Battalion Center Port Hueneme.

On 23 November 1996 the ship was diverted for a Search and Rescue mission to recover survivors from a downed U.S. Air Force C-130 off the coast of northern California.

In the company of two smaller boats Stethem patrolled the area around the crash for some twenty hours while engaged in recovery efforts, which earned the destroyer the U.S. Coast Guard Meritorious Unit Commendation Medal.

Stethem's port visits during her deployment included Singapore, Malaysia, Bahrain, Oman, the United Arab Emirates, Perth and Sydney.

After serving as command ship for Northern Persian Gulf Maritime Interception Operations for a second time, she transited the Strait of Hormuz on 13 August, and arrived home in San Diego 4 October 1999.

After port visits to Hawaii, Guam, Oman, Darwin and Cairns, Australia, American Samoa, Singapore, and Thailand, Stethem reported to the United States Fifth Fleet on 28 February 2001.

On 30 September 2001, Stethem entered into drydock for her third Selective Restricted Availability (SRA) at the Southwest Marine and Continental Maritime shipyards in San Diego.

In early February, Stethem anchored off the coast of Puerto Vallarta, Mexico; this was the first foreign port visit by any U.S. naval combatant since the terrorist attacks on 11 September 2001.

Returning to the site of her commissioning at the end of July, Stethem took part in the 60th Anniversary of Seabee Days in Port Hueneme, California, in honor of her namesake.

On 5 April 2003, Stethem successfully performed the first ever surface ship launch of a Block IV Tactical Tomahawk cruise missile, bringing it one step closer to fleet introduction.

After this successful engagement, Stethem celebrated by transiting north to make post calls at Juneau, Alaska and Victoria, British Columbia.

Returning from her trek up North in June, Stethem rested for one week and then put back to sea to serve as the opposition force against Pacific Fleet's first Expeditionary Strike Group, which was headed up by amphibious assault ship USS Peleliu.

On 2 July 2017, Stethem sailed within 12 nautical miles of Triton Island in the South China Sea while conducting freedom of navigation exercises.

[4] On 1 August 2017, while on routine patrol 140 miles west of Subic Bay, Philippines, one of Stethem's sailors was reported missing and presumed to have gone overboard.