In a rematch of the 2021 French Open decider, Djokovic swept to a 6-3 7-6(4) 7-6(5) victory at Rod Laver Arena to reclaim the world number one ranking and again deny Tsitsipas a maiden major crown.
The atmosphere was electric and the crowd often unruly as Serbian and Greek fans bayed in the terraces as if roaring on football teams.
But at the finish familiar chants of “Nole! Nole” won out as Djokovic stormed to a 5-0 lead in the final tiebreak and closed out the match with a thumping forehand down the line.
Djokovic’s record-equalling 22nd Grand Slam triumph, matching Rafa Nadal’s haul, was the ultimate redemption a year on from his sensational deportation from Australia on the eve of the Grand Slam due to his lack of COVID-19 vaccination.
“I have to say this has been the most challenging tournament I have played in my life,” said Djokovic as he cradled the Norman Brookes Challenge Cup.
“Not playing last year, coming back this year.
“This is probably the biggest victory in my life considering the circumstances.”
After sealing match point, the 35-year-old Serb tapped his temple then his heart before walking to the net to shake hands with Tsitsipas.
He climbed into his players box and unleashed a primal scream before breaking down in tears while hugging his mum.
The tears were still flowing after he returned to his chair and sat with a towel draped over his head.
Despite saying repeatedly he bore no grudges over his deportation, Djokovic left no one in doubt that it would fuel his success.
He had plenty of other spurs at this tournament, with heckling fans, scepticism about the severity of his hamstring injury and calls for his father Srdjan to be barred from Melbourne Park for mixing with Vladimir Putin supporters bearing banned Russian flags.
As in the semi-final, Srdjan did not take his seat in his son’s box but hugged him later off-court.
Djokovic came on court with only pressure tape on his left thigh where before it was strapped, an ominous sign for Tsitsipas.
Third seed Tsitsipas, who gave up a two-set lead to lose to Djokovic at Roland Garros in 2021, had his chances on Sunday, including a set point in the second set, but was unable to convert.
“Novak brings the best out of me and these are the matches I’ve been working my entire life for,” he said in a gracious runners-up speech.
“He’s the greatest that has held a tennis racket.”
Facing a man in his 33rd Grand Slam final, Tsitsipas, in his second, had a poor start.
He double-faulted to drop serve in the fourth game and in a flash Djokovic was 4-1 ahead, soon wrapping up the set with a wide, kicking serve.
Tsitsipas steadied on serve and found some respite.
He had Djokovic tumbling on the court in pursuit of a backhand at 3-3 in the second set and frustrated with his resilience.
A riled Djokovic began mouthing off at his non-plussed coach Goran Ivanisevic in the box.
He coughed up a set point at 5-4 with a backhand error but saved it with a forehand winner down the line.
The crowd grew febrile in a chaotic tiebreak, with one fan belting out a song during a rally at 4-4.
Tsitsipas cracked, hitting long twice, and Djokovic sealed the set as he did the first, with a wide serve.
With the match slipping from his grasp, Tsitsipas needed a bit of luck and found some quickly as Djokovic dropped serve with a messy opening game in the third set.
But again the chance was lost when he missed a forehand with an open court begging.
The Greek barked expletives and Djokovic pounced, breaking straight back with a patch of brilliant shot-making.
From there, the Serb locked down with trademark control before bashing a forehand down the line to raise three match points in the final tiebreak.
He squandered one with an errant backhand and Tsitsipas saved the second with a huge serve, but Djokovic made no mistake on the third.
With his entourage having changed into T-shirts emblazoned with “10”, Djokovic held the winner’s trophy aloft once more, 15 years after hoisting it for the first time as a 20-year-old in 2008.
The Serb has no plans to slow down.
“I really don’t want to stop here … Of course, 35 is not 25,” he said. “But I still feel there is time ahead of me.”
Earlier at Rod Laver Arena, top-seeded Czech duo Barbora Krejcikova and Katerina Siniakova won the women’s doubles title, beating Japan’s Shuko Aoyama and Ena Shibahara 6-4 6-3.