North Yorkshire Police said it received a report that a man had entered the river near the Q-Park car park in Garden Place at about 4pm on Saturday.
A spokesman said: "He was pulled from the river by a member of the public and taken to York Hospital for treatment.
"Sadly, the man, who was in his 20s and from York, died in hospital the following day."
The force said it was not yet in a position to identify the man and enquiries were continuing into how he came to be in the river.
Anyone who has information that could help the investigation is asked to contact North Yorkshire Police on 101, quoting reference number 12180133086.