The Serbian world number one swept to a 6-1, 7-5, 7-6 (7/3) victory in two hours, 53 minutes to hand Murray his fifth defeat in the Melbourne Park final.
Djokovic equalled the tally of Australia’s Roy Emerson, who won the tournament six times between 1961 and 1967, an achievement that has gone unmatched in the 49 years since.
It was also Djokovic’s 11th Grand Slam title, and he moved into equal fifth place with Rod Laver and Bjorn Borg behind 17-time leader Roger Federer.
Djokovic paid tribute to his vanquished rival, telling the crowd at the presentation: “Tough luck tonight Andy, you are a great champion, you’re a great friend, a great person.
“He’s very professional and committed to this sport, so I am sure in the future he is going to have more opportunities to play for this trophy.”
Djokovic underlined his status as the dominant force in Melbourne, after downing Jo-Wilfried Tsonga to win his first major title in 2008 and beating Rafael Nadal in an epic final in 2012, along with his four wins over Murray in 2011, 2013, 2015 and now 2016.
Djokovic also extended his Grand Slam winning streak to 21 matches, and he has not lost a match at the majors since he was defeated by Stan Wawrinka in last year’s French Open final at Roland Garros.
While Djokovic was further enhancing his reputation, Murray has the unwanted statistic of becoming only the second man in the post-1968 Open Era to lose five Grand Slam finals at any one major.
Ivan Lendl, Murray’s former coach, lost five finals at the US Open in 1982-1984 and 1988-1989, before winning at Flushing Meadows in 1985-1987.
Murray had tears in his eyes at the presentation when he thanked his pregnant wife Kim Sears, who is due to give birth to their first child in the coming weeks.
“You’ve been a legend for the last two weeks. Thank you so much for all of your support and I’ll be on the next plane home,” he said in a faltering voice.
Djokovic faced a break point in his opening service game but then went on a blazing run, breaking Murray’s serve twice to claim opening set in 30 minutes.
It took the Scot until the sixth game to hit his first winner and end a 14-game winning sequence by Djokovic in his meetings with Murray.
Murray survived four break points to hold serve in a marathon 12-minute third game as he tried to stay in the second set against the pressing Serb.
But Djokovic gained another psychological breakthrough with a service break in the seventh game after Murray overhit a forehand to trail 4-3.
Fighting Murray broke back in the following game with his backhand clipping the baseline, which was confirmed by Djokovic’s challenge.
Murray fought off two break points in a fiercely-contested ninth game in a war of the attrition between the two long-time rivals.
But Djokovic fought back from 0-40 down to break Murray’s serve for a fourth time featuring one exhaustive 36-shot rally to lead 6-5 and serve for the second set.
The Serb claimed a two sets to love lead after winning an 80-minute battle for the second set, leaving Murray with it all to do.
Djokovic tightened the noose with another service break in the first game of the final set, with Murray looking at the herculean task taking the final to five sets.
Murray broke back in the sixth game but in the tiebreaker the Scot served two double-faults as Djokovic steamed to five match points, and won on his third match point with an ace.
It was another big statement from Djokovic against his major rivals after beating Rafael Nadal 6-1, 6-2 at Doha and convincingly beating Roger Federer in the Melbourne semi-finals.