The ship is headed for Southampton in southern England and is to embark on its official maiden voyage on May 22 to its new home port of Barcelona.
The floating town, which cost close to one billion euros (dollars), has 16 decks and will be able to carry 6,360 passengers and 2,100 crew members.
The crowd waved, cheered and clapped as the boat -- built for the US-based Royal Caribbean Cruises Ltd (RCCL) -- eased away from France.
As the massive boat pulled away from a shipyard in Saint-Nazaire, where it was built on France's Atlantic shore, some 70,000 people watched from along the coast, local authorities said.
At 66 metres (217 feet), it is the widest cruise ship ever built, while its 362-metre length makes it 50 metres longer than the height of the Eiffel Tower.
Harmony of the Seas: World's largest cruise sets sail for UK