In March 2003, Antietam was assigned to Carrier Group Three.

Antietam operated out of her home port of San Diego, Calif. In 2009, she completed a six-month deployment, leaving San Diego in January 2009, and returning home in July 2009.
Stops along the way included Hong Kong, Japan, South Korea, Singapore, Thailand, Guam, and Hawaii.

From January to August 2007, Antietam deployed to the Persian Gulf.
 During that seven-month deployment, she visited Dubai, Singapore, Hong Kong, and Pearl Harbor before returning to home port.

From February to August 2005, Antietam completed a circumnavigation of the Earth, leaving San Diego to the west and returning home by way of the east.
During the deployment, she had an extended stay in the Persian Gulf as part of Operation Iraqi Freedom.
On the return to home port, she disembarked nearly a third of her active personnel in Florida to make room for family and friends of the remaining crew, who embarked in Puerto Vallarta, Mexico, to take part in a friends and family "tiger cruise" back to San Diego.

In February 2013, Antietam relieved USS Cowpens in a "hull-swap" at Yokosuka, Japan, in which the two crews swapped ships.
Cowpens, previously deployed to Yokosuka, was then homeported at Naval Base San Diego, California, while Antietam took up her new homeport at Yokosuka.

On 31 January 2017,  Antietam ran aground in Tokyo Bay near her home port of Yokosuka, Japan.
Antietam was anchored off the coast in 30-knot winds and a strong tide when the crew noticed the ship was dragging its anchor.
They got the ship underway, but shortly after doing so, they felt the ship shudder as it lost all pitch control in both propellers.
They had run aground on a shoal with damage to both propellers and one of the propeller hubs, causing 1,100 US gallons (4,200 l) of hydraulic oil to leak into the water.
No personnel were injured during the incident.
Repairs were expected to cost at least $4.2 million.

On 22 October 2018, she transited the Taiwan Strait along with USS Curtis Wilbur.
On 24–25 July 2019, she again transited the Taiwan Strait.
On 19-20 September 2019 she transited the Taiwan Strait a third time.
In March 2003, Antietam was assigned to Carrier Group Three.
Antietam operated out of her home port of San Diego, Calif. In 2009, she completed a six-month deployment, leaving San Diego in January 2009, and returning home in July 2009. Stops along the way included Hong Kong, Japan, South Korea, Singapore, Thailand, Guam, and Hawaii.
From January to August 2007, Antietam deployed to the Persian Gulf.  During that seven-month deployment, she visited Dubai, Singapore, Hong Kong, and Pearl Harbor before returning to home port.
From February to August 2005, Antietam completed a circumnavigation of the Earth, leaving San Diego to the west and returning home by way of the east. During the deployment, she had an extended stay in the Persian Gulf as part of Operation Iraqi Freedom. On the return to home port, she disembarked nearly a third of her active personnel in Florida to make room for family and friends of the remaining crew, who embarked in Puerto Vallarta, Mexico, to take part in a friends and family "tiger cruise" back to San Diego.
In February 2013, Antietam relieved USS Cowpens in a "hull-swap" at Yokosuka, Japan, in which the two crews swapped ships. Cowpens, previously deployed to Yokosuka, was then homeported at Naval Base San Diego, California, while Antietam took up her new homeport at Yokosuka.
On 31 January 2017,  Antietam ran aground in Tokyo Bay near her home port of Yokosuka, Japan. Antietam was anchored off the coast in 30-knot winds and a strong tide when the crew noticed the ship was dragging its anchor. They got the ship underway, but shortly after doing so, they felt the ship shudder as it lost all pitch control in both propellers. They had run aground on a shoal with damage to both propellers and one of the propeller hubs, causing 1,100 US gallons (4,200 l) of hydraulic oil to leak into the water. No personnel were injured during the incident. Repairs were expected to cost at least $4.2 million.
On 22 October 2018, she transited the Taiwan Strait along with USS Curtis Wilbur. On 24–25 July 2019, she again transited the Taiwan Strait. On 19-20 September 2019 she transited the Taiwan Strait a third time.
USS Antietam (CG-54)