The 95-year-old monarch stepped aboard the HMS Queen Elizabeth in Portsmouth, seven years after she named the vessel alongside her late husband Prince Philip, who died last month.
The 65,000-ton warship will carry eight British F-35B fighter jets and 10 US Marine Corps F-35s as well as 250 US Marines as part of a 1,700-strong crew.
It will lead the flotilla alongside two destroyers, two frigates, a submarine and two support ships on its journey of 26,000 nautical miles over 28 weeks. The group will be joined by a US Navy destroyer and a frigate from the Dutch navy.
The group will sail through the contested South China Sea, parts of which are claimed by China and Southeast Asian countries, on its way to the Philippine Sea. The ships will also stop in India and Singapore.
British Prime Minister Boris Johnson has said the deployment will help to project British soft power such as a belief in democracy and the rule of law.