[24] HST was authorized and laid down as USS United States, but her name was changed in February 1995 at the direction of then-Secretary of the Navy John H. Dalton.

Three Newport News ship workers died during construction when a pump room filled with methane and hydrogen sulfide gases during a sewage leak on 12 July 1997.

The ship successfully completed builder's sea trial on 11 June 1998 after a short delay due to noise issues in one of the reactor closure heads.

In August 1998, Harry S. Truman left port for the first time to conduct certifications to test her ability to recover and launch aircraft successfully.

[24] On 26 December 2000, Harry S. Truman transited the Suez Canal "in support of Operation Southern Watch" with Carrier Air Wing Three flying 869 combat sorties, including a strike on Iraqi integrated air defense system sites, in a sanctioned response to Iraqi surface-to-air missile fire against United Nations Security Council coalition forces.

The ship called at Naples, Italy, and participated in Operation Majestic Eagle in the eastern Atlantic Ocean before returning to NNSY on 25 July.

[32] On 1 October 2004, as part of a Navy-wide series of redesignations, Harry S. Truman's immediate superior in command changed to Carrier Strike Group Ten.

The ship set out from Norfolk on her third extended deployment on 13 October 2004, and visited Souda Bay, Crete, before relieving USS John F. Kennedy on 20 November in the Persian Gulf.

Harry S. Truman and CVW-3 launched 2,577 sorties, totaling nearly 13,000 flight hours, flying combat missions over Iraq and maritime security operations before being relieved by USS Carl Vinson Carrier Strike Group in the Persian Gulf on 19 March 2005.

Despite plans to cross the equator and visit South Africa, diplomatic issues caused her, instead, to transit the Suez Canal, stopping in Portsmouth, England, prior to returning home on 18 April 2005.

[34] The ship received many system upgrades, and underwent preventive maintenance to repair minor weld defects originating from the initial construction of the reactor plants.

On 20 June, the ship visited four ports during her 213 days at sea, including Marseille, France; Dubai, U.A.E; Manama, Bahrain; and Souda Bay, Crete, before returning to the United States on 21 December.

During the deployment, Harry S. Truman traveled more than 50,000 nautical miles and flew more than 10,000 sorties in support of Operations Enduring Freedom and New Dawn.

[46] On 7 April, Norfolk Naval Shipyard completed the ship's nuclear power plant modernization and testing was to begin to ensure her readiness for sea trials lasting 90 days.

[50] On 22 July, Harry S. Truman left for an extended deployment to the 5th Fleet area of responsibility, and settled into her mission of supporting Operation Enduring Freedom and the coalition of troops on the ground in Afghanistan.

On 14 February, the Commander, Naval Air Force U.S. Atlantic Fleet named Harry S. Truman as the East Coast aircraft carrierBattle "E" award winner.

[53] On 16 November, Harry S. Truman, assigned with Carrier Air Wing Seven, began a scheduled deployment to the U.S. 6th and 5th Fleet areas of operation.

[54] On 21 December, Djibouti President Ismail Omar Guelleh visited USS Harry S. Truman stationed near the Yemeni island of Berim.

[55] On 26 December while transiting the Strait of Hormuz, several unguided rockets fired by Iran landed about 1,500 yards (1,400 m) away from Harry S. Truman, which was traveling with the destroyer Bulkeley and the Provence.

[57] On 12 January, an unarmed Iranian drone flew directly over Harry S. Truman in international waters and took "precise" photos, according to state television in the Islamic Republic.

[60] On 21 July, the refit was concluded and was followed by various training exercises placing emphasis on damage control, flight deck operations, and simulated combat at-sea.

[65] On 27 February, the Pentagon announced that Harry S. Truman's midlife refueling and overhaul, tentatively scheduled for 2024, may be cancelled and the ship instead retired early as a cost-saving measure.

[66] Congress prevented the Navy from taking the same action with sister ship George Washington in 2016,[67] as well as the White House, as President Donald Trump had promised to increase the carrier fleet to 12.

She was originally planned to transit the Suez Canal into the Middle East, but in light of the standoff between Russia and Ukraine in late 2021 escalating, the carrier was ordered to stay in the Mediterranean.

[76] On 8 August 2022, the United States Sixth Fleet announced the lost aircraft had been recovered from a depth of 9,500 feet (2,900 m) using a remotely operated CURV-21 recovery vehicle.

[78] The aircraft was loaded aboard Military Sealift Command roll-on/roll-off ship USNS Mendonca at the Port of Augusta on 16 August to be transported back to the United States.

[80][81] On 21 November, the Navy accepted Auxiliary Personnel Lighter 68 (APL68), with around 600 berths, saying it would support the impending Harry S. Truman carrier repair cycle.

[89] Harry S. Truman was involved in a collision with the Panamanian-flagged merchant vessel Besiktas-M at approximately 11:46 p.m. local time on 12 February, while operating in the vicinity of Port Said, Egypt, in the Mediterranean Sea.