The pair have a history of producing some scintillating matches on the biggest of stages and there is every indication that this will be the case again come Monday evening under the floodlights of the famous Arthur Ashe Stadium in New York.
Sports Mole takes a look at the two players ahead of their showdown in the Big Apple.
Previous best at US Open:
Murray: F 2008
Djokovic: W 2011
Record in 2012:
Murray: W40, L11
Djokovic: W54, L10
Head to head: Murray 6-8 Djokovic
Last meeting: Murray 7-5 7-5 Djokovic - Olympic semi-final, August 2012
Where will the match be won and lost?
Djokovic has been in imperious form at this year's tournament, dropping only one set on his way to a third consecutive final.
In contrast, Murray has made life typically difficult for himself at Flushing Meadows, especially in his matches against Marin Cilic and Tomas Berdych.
The defending champion is one of the game's great counter-punchers which means that Murray's offensive strategy will have to be pretty much perfect if he is to make any progress.
However, the Scot's defensive displays have been as good as anyone's in the Big Apple this year and he will be quite happy to soak up any pressure before ripping a winner past his opponent.
That said, he will need to be wary of Djokovic's variety from all sides of the court, with the Serb's ability to pull out a winner from the most ridiculous of situations.
Sports Mole says: Andy Murray to clinch his maiden Grand Slam title.