After a match lasting almost five hours, he became the first British winner of a Grand Slam men's singles title for 76 years, eventually triumphing 7-6 (12-10), 7-5, 2-6, 3-6, 6-2.
The success of the man from Dunblane came exactly 79 years to the day that Fred Perry also won the US Open. Perry was the last British men's singles champion three years later.
Murray, who lost to Djokovic in the Australian Open final last year, is the first man ever to win Olympic singles gold and the US Open title in the same year and and emulated coach Ivan Lendl in winning his first grand slam trophy at his fifth attempt.
For the fifth year in a row the men's final had been put back a day because of the threat of a tornado on Saturday, which disrupted the semi-finals.
It was not as windy today but it was far from calm either, which potentially was a positive for Murray.
The Scot had coped well with the conditions in beating Tomas Berdych while Djokovic struggled against David Ferrer before the match was postponed.
He was a different player when it was completed yesterday, though, and went into the final unbeaten on hard courts at a grand slam for two years.
Murray needed to start well and her certainly did, Djokovic again looking unsure in the wind as he was broken to love.
But Murray handed the break straight back and then missed four chances to break for a second time.
But, that disappointment aside, it was certainly the third seed who had started better and he moved ahead again at 3-2 when Djokovic threw in two double faults.
One titanic rally in the next game highlighted why the Serb is a five-time grand slam champion as Murray pummelled his opponent but could not break down his legendary defences.
He held but Djokovic levelled again two games later, and the Serb seemed to be becoming more confident in his shots.
The James Bond theme played as Sir Sean Connery was shown on the big screen along with actor Kevin Spacey while Sir Alex Ferguson also arrived, with the Manchester United manager sitting in Murray's box.
The two Scottish knights had gatecrashed Murray's press conference on Friday to congratulate their countryman, and he certainly needed the support now.
At 5-6, Djokovic piled the pressure on with his relentless groundstrokes but Murray stood firm to force a tie-break.
The rallies got ever longer and more intense. Djokovic seemed in control but Murray dug in and had the first set point.
Djokovic was rock solid on that one but uncharacteristically fired a backhand long to give the Scot a chance on his own serve only for Murray to net a backhand.
Set points three, four and five disappeared, too, all of them for Murray, but on the sixth chance he found a serve that even Djokovic could not get back in court to take it 12-10.
It was only the second set Murray had ever won in a grand slam final and, like the Wimbledon final against Roger Federer, it was the opening set he took.
He went on to lose the next three that day but he made the perfect start to the second set here as, like he had in the opener, Djokovic dropped his serve to love.
The Serb, who has won four of the last seven grand slam titles, looked a little rattled, and he dropped his serve again to hand Murray a 4-0 lead.
After the tension of the first set, it was a shock, but Murray was playing with confidence and poise in the tricky conditions.
Djokovic rallied to retrieve one break and forced Murray to serve out the set, and there the third seed faltered, netting three times.
He saved one break point but hooked a wind-assisted forehand well over the baseline on the second.
It was a big blow after he had held such a commanding lead, and Djokovic was now well and truly out of his slump and pushing to level the match.
But Murray held for 6-5, celebrating with a yell of "come on", and it proved a key moment when in the next game Djokovic missed a smash to hand his opponent two set points.
Arthur Ashe roared and, although he saved one with a good serve, a forehand wide sealed it for Murray 7-5.
This was now uncharted territory for Murray but there was still an awfully long way to go, with Djokovic having demonstrated his ability to come back from seemingly impossible positions many times in the last two years.
Murray also has a tendency to dip at the start of third sets and, although he got out of jail in the first game, in the third he could not prevent Djokovic breaking through.
The Scot had his chance to hit back in the sixth game but Djokovic saved two break points, roaring himself on as Murray's scrambled backhand landed long on the second.
Murray, too, was shouting at himself and he gave an insight into his mental state by revealing his legs felt like jelly, and a poor game allowed the Serb to take a 5-2 lead.
And this time there was no twist as Djokovic clinched his first set of the match 6-2 with a rock solid smash.
Murray badly needed a good start to the fourth set but he did not get it, the Scot's forehand beginning to regularly find the net as Djokovic broke through again.
At least Murray saved a break point to prevent his opponent taking a 3-0 lead, but he was beginning to look rather disconsolate.
He showed more aggression in the next game to force a break point but Djokovic, fired up by a code violation for taking too long before serving, held on.
Murray was playing well again, though, and had Djokovic literally on his backside in one astonishing point in the sixth game.
Still the break back would not come, Djokovic serving better than he had at any point all evening, and as the match entered its fifth hour the Serb had his first set point on the Murray serve, taking it 6-3 when his opponent fired a backhand long.
No one had come back from two sets down to win the US Open since Pancho Gonzalez in 1949 but Djokovic had both momentum and experience on his side.
However, there was a twist at the start of the decider when Murray got a bit of luck with a net cord and a potentially crucial break.
The 25-year-old then showed defensive skills worthy of his opponent to hold for 2-0, whipping up the crowd into a frenzy.
Suddenly Djokovic looked weary and Murray was half way there when the Serb netted a simple forehand to hand his opponent a second straight break.
He had, of course, been in a similar position in the second set only for Djokovic to hit back, and it was deja vu as the Serb pulled one break back straight away.
It was torture for both players' supporters, but some brilliant serving from Murray gave him breathing space, and then suddenly he was a game away.
Djokovic made his opponent wait for the biggest service game of his life as he received treatment to his right thigh, drawing boos from the crowd who clearly felt it was unsporting.
But Murray gave the best response, setting up three championship points and taking the second when Djokovic drilled a forehand long.
After four hours and 54 minutes, Murray had done it, sinking to his knees in delight, disbelief and sheer exhaustion as his family and friends hugged each other and cried.