The ships will engage in security exercises in the Pacific and Indian oceans.
The San Diego harbor will be less two ships after Thursday.
Aircraft carrier Carl Vinson and destroyer Wayne E. Meyer will set course for assignments in the Pacific and Indian oceans.
The Carl Vinson will head a fleet of ships including the Meyer and cruiser Lake Champlain along with Hawaiian-based destroyer Michael Murphy.
This strike group will take with it 7,500 sailors and airman under Carrier Air Wing 2.
With a focus on security cooperation efforts, and maritime security operations, this tactical force will conduct exercises with allied nations in the western Pacific and Indian oceans.
Named after a Georgian who served in Congress for half a century, the Vinson is probably best known for receiving the body of Osama Bin Laden after he was killed in Pakistan in 2011.