Witnesses reported seeing the man, who is believed to be in his late teens to early 20s, fall from the middle arch of the Ouse Bridge at about 03:15 BST, North Yorkshire Police said.
Officers said onlookers had tried to throw a lifebelt to the young man before emergency services arrived.
It is thought he got into difficulty and was unable to swim to safety.
A search is under way for a man who was seen falling from a bridge into the River Ouse in York.