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The world number one's 7-5 6-2 6-2 win on his favourite court secured his 18th Grand Slam title, bringing him within tantalising reach of Roger Federer and Rafa Nadal's all-time men's record of 20.
"I would like to thank Rod Laver Arena. I love you each year more and more. It's been a love affair that keeps growing. Thank you so much," Djokovic said as he cradled the Norman Brookes Challenge Cup once again.
With a fortune spent to put on a biosecure tournament amid the Covid-19 pandemic, Djokovic came into the Grand Slam under fire after offending the Australian public for petitioning organisers to ease quarantine conditions for players.
He suffered a painful abdominal injury in the first week and had to manage it through the second.
But those challenges were drowned out in the roars of his fans as he thrashed fourth seed Medvedev in a bearpit atmosphere.
"It has been definitely emotionally the most challenging Grand Slam that I ever had with everything that was happening, injury, off-the-court stuff, quarantines," he said.
"It has been, least to say, a roller-coaster ride in the last four weeks."
Much like Dominic Thiem in last year's final, Djokovic faced an opponent desperate for a seat at the Grand Slam table.
Unlike Thiem, who pushed Djokovic to five sets, Medvedev never threatened in his second major final.
Djokovic made a mockery of the Russian's 20-match winning streak and his pre-match barb that all the pressure was on the champion.
He broke him seven times and closed out the one-sided contest with a net-rush and a brilliant leaping volley.
Having extended his unbeaten record in nine finals at Melbourne Park, Djokovic bellowed in triumph and wrapped his team in a group hug.
Nadal is the only man to have won more titles at a single Grand Slam, with his 13 at the French Open. Djokovic now has won six majors after the age of 30, equalling Nadal's record.
Djokovic had said pre-match that Medvedev was the man to beat but it all seemed like mental games when the Serb shot out to a 3-0 lead.
Medvedev rallied to 3-3, though, edging Djokovic in fierce baseline exchanges.
Djokovic switched tactics, pulling the Russian to the net, his least favourite part of the court.
The ploy paid off as Djokovic ripped a backhand passing shot for three set points and took it when a flustered Medvedev thumped a forehand into the net.
While Medvedev broke Djokovic early in the second set, the Russian handed the break back with an error-strewn game.
Play was suspended briefly mid-point at 2-1 after a protester yelled "free the refugees" during play before being ejected to cheers.
Medvedev then dropped serve in a hurry and smashed his racket in fury after Djokovic marched on to a 5-2 lead.
The crowd grew unruly and were repeatedly upbraided by the chair umpire as Medvedev sank deeper into a funk.
He slapped a forehand long to concede two set points before being almost knocked off his feet by a Djokovic return.
Worse was to come for Medvedev as he was broken twice in succession, a weak volley into the net handing Djokovic a 3-0 lead in the third set.
With a humiliation threatening, Medvedev swung hard in a final stand but found no way through Djokovic's stonewall defence.
After winning an epic rally to be within a game of victory, Djokovic threw an icy gaze at the Russian and tapped his temple as he walked to his chair before closing it out.
Medvedev was left to rue another chance gone begging, having lost to Rafa Nadal in a five-set thriller at the 2019 US Open.
He likened the Big Three of Djokovic, Nadal and Federer to "Cyborgs of tennis, in a good way."
"I guess he's (Djokovic) the King of Melbourne, even if I don't like these words. What else can we say? He won here nine out of nine times."