In windy conditions at Flushing Meadows, Murray was able to fight off a determined effort from the defending champion in the longest match in U.S. Open title history (four hours and 54 minutes), 7-6 7-5 2-6 3-6 6-2.
Serving for the win, the Scottish star reacted with surreal appreciation when Djokovic's final shot went long. Murray would walk around the court in somewhat of a haze to the standing audience.
After breaking Djokovic's serve for the second time in the fifth set, Murray walked to his chair expressionless, not acknowledging that a historic victory was firmly in his grasp.
Indeed, Murray's trepidation about a premature celebration was wise, as Djokovic would battle back with a break. Djokovic decided to serve and volley at one point in the fifth game. It was the first of the match, as both baseline players wailed on the ball for more than four and half hours and likely surprised Murray.
It was a gut-wrenching effort for both men, and neither appeared ready to concede anything. After a tremendous sequence of shots in the fifth set, Djokovic pumped his fists. The normally excitable tennis star showed less emotion than he usually does, which is likely a testament to his opponent's resilience and gravity of the match.
Murray was seen pumping his fist with confidence as he sensed his first title was just minutes away, and as Djokovic was battling leg cramps with the score 5-2. Djokovic received treatment, but he didn't seem to fully recover.
The very first set lasted one hour and 27 minutes and was filled with exciting moments. At one point, a feverish exchange in the service box resulted with Murray hitting a passing shot about a foot wide, and the Scot would pound his strings in frustration with his wrist as he fell to a triple-break point.
Murray would win the next point, but Djokovic would win the game on the ensuing point despite Murray's hustling efforts to return multiple overheads from the hard-hitting Serb.
In the first-set tie-breaker, Djokovic handed Murray a chance to win the set with a careless ground stroke that went long. Murray failed to take advantage of it, as the following point saw him rip a routine approach shot into the net.
"This is unbelievable," said broadcaster and tennis legend John McEnroe, following a rally that had 33 shots and ended with Murray lobbing a ball wide over Djokovic.
The first-set tie-breaker would go to Murray after 24 minutes of exhausting tennis.
Murray would win the second set, due in part to his superb defense.
But Djokovic would storm back. The Serbian star would win the following two sets. Murray would try to hold off Djokovic's determined effort.
It was one of the most amazing things you will see in this sport," said McEnroe, as the match was in its final game.