Antietam was laid down by the Litton-Ingalls Shipbuilding Corporation at Pascagoula, Mississippi, on 15 November 1984, launched on 14 February 1986, and commissioned on 6 June 1987 in Baltimore, Maryland.

She also carries two Sikorsky SH-60 Seahawk LAMPS helicopters, capable of multiple missions, but primarily equipped for antisubmarine warfare (ASW).

Antietam was one of the first vessels to take part in Operation Desert Shield, along with the rest of the USS Independence Battlegroup in August 1990, in response to the Invasion of Kuwait.

[2] According to an interview in 2007 BBC documentary, The Last Flight to Kuwait, Lawrence Eddingfield, who was captain at that time stated that the vessel was involved in a helicopter rescue of two British SAS troops who had arrived on BA 149 during the invasion.

From February to August 2005, Antietam completed a circumnavigation of Earth, leaving San Diego to the west and returning home by way of the east.

During that seven-month deployment, she visited Dubai, Singapore, Hong Kong, and Pearl Harbor before returning to home port.

[16] On 25 June 2023, Antietam, along with aircraft carrier Ronald Reagan and cruiser Robert Smalls, paid a visit to Vietnam.

McCampbell will replace USS Antietam (CG 54), which will depart Yokosuka, Japan, in January, after 11 years of forward deployed service and move to Pearl Harbor, Hawaii, as part of a scheduled rotation of forces in the Pacific.