In early April 2004, Navy officials announced plans to deploy Fitzgerald, 14 other destroyers, and three cruisers to counter ballistic missile threats worldwide.

The next month, she took part in a personnel exchange known as "Super Swap", taking aboard 141 sailors from the destroyer O'Brien and transferring 95 to join the soon-to-be-decommissioned ship's decommissioning unit.

In March 2011, in company with the aircraft carrier Ronald Reagan, Fitzgerald was deployed off northeastern Honshu, Japan, to assist with relief efforts after the 2011 Tōhoku earthquake and tsunami.

[9][10] On 1 June 2017, Fitzgerald, operating out of Yokosuka Naval Base, was noted for participating in routine exercises with Japan that were described in the media as a show of force to North Korea.

In May 2022, Fitzgerald was homeported at Naval Station San Diego and a part of Destroyer Squadron 2, along with Carrier Strike Group 3 led by USS Abraham Lincoln.

ERM v4, developed by Fathom5, replaces the previous Integrated Condition Assessment System (ICAS) and is intended to support the Navy's efforts to maintain a more readily available fleet, particularly in high-demand situations.

[29] Including costs for planned service life extension and other upgrades, repairs for the damage to Fitzgerald are expected to run about $368.7 million,[30] and will take over a year.

[34] In late August 2017, it was reported that the destroyer will be transported by the Dockwise heavy-lift ship MV Transshelf to Huntington Ingalls Industries’ shipyard in Pascagoula.

[41] In August 2019, the Japan Transport Safety Board's final report concluded distraction and incomplete radar information aboard the US Navy vessel caused the accident.