Nitze, who was 97 years old at the time, was present at the christening, thus adding the destroyer to the list of U.S. military vessels named after living Americans.

Nitze, homeported in Norfolk, Virginia, went on her maiden deployment in January 2007 as part of the USS Bataan Expeditionary Strike Group, returning home on 3 July 2007.

On 12 September 2008, Nitze departed Norfolk for a seven-month deployment with Carrier Strike Group Two, led by USS Theodore Roosevelt, returning on 18 April 2009.

From 12 March to 4 November 2012, Nitze completed her third deployment to the Fifth Fleet Area of Responsibility with the USS Enterprise Battlegroup (CCSG 12).

On 24 August 2016, Nitze was conducting a routine transit near the Strait of Hormuz, accompanied by USS Mason, when the ship was approached by four small patrol craft of the Iranian Revolutionary Guard Corps.