Crew members cheered as tourists embarked on the vessel, which set sail with 1195 passengers.
Richard Fain, chairman of Celebrity Cruises' parent company RCG-Royal Caribbean Group, spoke at a media reception at Port Everglades' "Terminal 25" before embarkation.
"This is a momentous sailing and one that we have been preparing for a long time.
"It's not only a huge honor to be the first ship back in the water, leading the industry in the long-awaited return to U.S.-based cruising, it's also an incredible achievement and testament to the tireless efforts of our shoreside team and onboard crew."
Celebrity Edge's departure was momentous not only for the brand but for Port Everglades, which suffered a more than 50% loss in revenue last year primarily from the industry's shutdown due to the Coronavirus crisis. Ship cruises typically generate ~USD 60 million in revenue annually for Port Everglades.