Harmony of the Seas left the western port of Saint Nazaire on Thursday afternoon and, if all goes well, it will not return until Sunday morning.
The purpose of the voyage is mainly to test the power on the boat and how well it manoeuvres, which, given it weighs some 227,000 tonnes and measures 362 metres in length, will be interesting to see.
For months, tourists have been allowed on board to gape at the innards of the ship, which has 16 decks.
Three pilots, who have trained on a simulator in nearby Nantes for the past year, helped the captain in the tricky manoeuvres needed to guide the hulking ship out of the Saint-Nazaire estuary.
The tugs first helped the ship back out of its berth before turning it around and then guiding it out to the open sea.
The pilots will leave the vessel once it is 20 kilometres (12 miles) out at sea.
There will be no passengers on board during the test voyage, just 500 staff.
If testing goes as planned, the boat will eventually head to British port of Southampton in May, from where it will set sail for Barcelona for its first cruise around the Mediterranean.
Harmony of the Seas makes the Titanic, which measured 269 metres, look like a little pleasure boat - and it is even 50 metres longer than the Eiffel Tower.
Harmony is also a metre wider than the current twin ocean-going monsters of the pleasure cruise world, which are also 362 metres long.
"Allure of the Seas" and "Oasis of the Seas", the world's biggest cruise ships in current service, are 65 metres wide and come in at 225,000 tonnes a piece. All three belong to Royal Caribbean International cruise lines.
The ship will have room for some 6,360 passengers and 2,100 staff members.
The city's STX France shipyards began building the one-billion-euro ($1.1 billion) mammoth for US shipbuilder Royal Caribbean International (RCI) in September 2013.