[1] On 6 April 2000, Anzio, along with another cruiser and the aircraft carrier Dwight D. Eisenhower, was participating in an exercise in the Eastern Mediterranean Sea, about 250 miles (400 km) off the coast of Israel.

Ordered first to the eastern Mediterranean Sea for the initial phase of President George W. Bush's Shock and Awe strategy (during which the U.S. Navy deployed to defeat the Iraq military before ground forces were sent in).

After President Bush announced major combat had concluded in the Iraq War, on 1 May 2003, Anzio was relieved of her duties, returning home on 3 July 2003, after 175 days at sea.

[12][13] On 13 January 2016, ten U.S. Navy sailors were picked up by Anzio for transport and medical evaluations after being held in Iranian custody.

"The evidence suggests that they unintentionally entered the Iranian waters because of the failure of their navigational system," Islamic Revolutionary Guard Corps spokesman Ramazan Sharif said on Press TV.