The child and her family from Indiana were vacationing onboard the 'Freedom of the Seas' cruise ship.
Reports say her grandfather slipped and fell into the window while holding her, resulting the child to plunge from the 11th deck.
Witness passengers said they had heard a 'cry of pain' from the girl's mother, international media report.
She died in hospital shortly afterwards as a result. An investigation has begun to determine what happened.
Freedom of the Seas is the 15th largest passenger ship in the world, able to accommodate 5,000 people.
The young girl is not the first to fall from the upper decks of a cruise ship.
In 2012 a 14-month toddler fell from deck 12 to deck 11 on the Monarch of the Seas. The ship returned to Port Canaveral in Florida where the child recovered after medical care.