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.

In October 2009, Nitze was open to the public for tours in downtown Norfolk as part of the Navy Fleet Week celebration.

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.