Scotland’s world number two unsettled Serbia’s 2011 champion Djokovic from an epic opening game, coming back from breaks down in the second and third sets, before fending off a brave fightback while serving for the match as he claimed his finest career victory.
Murray won last year’s US Open to end what was then a 76-year wait for a British male Grand Slam champion; he is now the first Briton of either gender to win Wimbledon since Virginia Wade in 1977, and the first male since Fred Perry in 1936.
"It feels slightly different to last year," Murray said in reference to his tearful defeat in the 2012 final. "I don't know how I managed to get through that last game - losing three match points was unbelievable. It was hard to watch but imagine playing it!
"Novak has come back so many times from similar positions and he almost did it again."
The beaten world number one was typically sportsmanlike at the trophy presentation.
"Congratulations to Andy, who absolutely deserved this win - you played incredible tennis," Djokovic said. "I know how much it means to all of you guys, the whole country, well done.
"I'm aware of the pressure he gets, although I cannot imagine the extent not being in his shoes.
"It was an absolute pleasure and an honour to be part of this final."
Murray was exceptional at times but, by contrast, Djokovic had one of his worst games on Centre Court.
On the hottest day of the year in Britain, with the mercury soaring toward 30 degrees Celsius, the world's two best players produced some scorching sinew-stretching action from the start and the first three games alone lasted 20 minutes.
The opening salvo of the Centre Court clash lasted 20 strokes as Murray went up 0-40 on the Serb's serve but Djokovic produced staunch defence to stave off his opponent's attack.
The duo did trade breaks in the third and fourth games, with each Murray winner being greeted by a chorus of 15,000 roars.
Second seed Murray got another chance to break to love in the seventh game and this time he pounced as the 2011 champion surrendered his serve by slapping a backhand into the net.
A set that initially looked like lasting forever ended exactly on the hour mark as Djokovic whipped a service return wide to give Murray, runner-up to Roger Federer last year, the one-set cushion.
The battle between the two players who were born seven days apart in 1987 intensified in the second set as they went toe-to-toe from the baseline with 25-shot rallies being par for the course.
Djokovic, who survived a four hour 43 minute semi-final epic against Juan Martin Del Potro two days ago, showed his super-human ability to recover quickly as he ran down everything Murray could throw at him.
The Serb rattled Murray by going for the lines and broke for a 3-1 lead when Olympic champion Murray flicked a forehand into the net.
Even when Djokovic slipped and skidded flat on to his stomach while trying to chase down a Murray winner, the six-times Grand Slam champion appeared unfazed as he quickly got back on to his feet to extend his lead to 4-1.
But Murray, who trains in the intense Miami heat, showed off his iron-man conditioning as he stormed back to level at 4-4, a Djokovic double fault on break point down handing him the break back in the seventh game.
While the cheering crowd, which included British Prime Minister David Cameron, got behind a pumped up Murray, Djokovic simply exploded in anger in the 11th game.
Convinced that Murray had gone long mid-rally at 15-15, he screamed at umpire Mohamed Lahyani "Why? What's going on?" as he gesticulated wildly to show what he thought the linesman had failed to see.
Murray ignored the uproar to break the fuming Serb and soon had the fans roaring when he wrapped up the 69-minute second set with a 125mph thunderbolt ace.
The third set initially seemed a formality for Murray, who broke Djokovic early and almost sealed a double-break.
But two sloppy drop shots allowed the Serb to break back, with a rejuvenated Djokovic holding before winning the subsequent Murray service game as the Briton seemed to lose momentum.
Murray, however, has incredible mental and physical reserves and cancelled out that break with some intense hustling at the net, bringing it back with serve, which he held with a wonderful diving forehand off the baseline.
That was followed by a magnificent break for Murray, which boasted two astounding last-gasp winners, leaving him serving for the title.
Initially Djokovic saved three championship points as a nervy Murray’s serve deserted him, and the Serb even had three break-back points thanks to an unforced error to net from the Briton, a wonderful drop-shot off the net-cord and then a beautiful diving winner across the net.
But Murray saved them all, bringing up his fourth match point with some incredible fight at the baseline, his forehand pass forcing Djokovic to net a volley.
And, after his next serve was returned just inside the baseline, Murray was a spectator as Djokovic netted the follow up, sending Centre Court and an entire nation into raptures.