The defeat left Medvedev, 25, a leading member of the next generation, wondering how to overcome Djokovic, Rafael Nadal and Roger Federer, who have 58 major titles between them.
A strict vegetarian diet, spiritual guru and family hugging-sessions are among the unusual methods that have helped Novak Djokovic to take his place among the immortals of tennis.
Here's a look at Djokovic's incredible run of success and the records he has set on the way to becoming the undoubted king of Melbourne Park:
Novak Djokovic’s Australian Open dominance improved to 18-0 combined in semi-finals and finals. On Sunday, Daniil Medvedev joined the ranks of Roger Federer, Rafael Nadal, Andy Murray, Stan Wawrinka, Dominic Thiem, all of whom have lost to Djoko in semis or finals in Melbourne.
23-year-old Naomi Osaka won her fourth Slam from the last eight she's contested. She became only the third player after Monica Seles and Roger Federer to win their first four major finals
Osaka's triumph over Jennifer Brady in the Australian Open final was hailed in Japan, and beyond, as astronaut Soichi Noguchi wrote from space "Naomi Osaka, congratulations on the victory," with a gold-medal emoji.
Australian Open 2021: Jennifer Brady says winning a Slam no longer feels as improbable as 'going to Mars'
Brady reached the Melbourne final despite undergoing 14 days' hard quarantine in Australia, forced to stay in her room while other players were allowed out every day to train.
The 23-year-old's zen-like mentality and increased gravitas on and off the court have elevated her alongside Serena Williams to being the one of the most recognisable female athletes on the planet.
"I'm probably going to watch some anime... maybe (eat) pizza... and go to sleep," said Osaka after winning her fourth Grand Slam title.
Naomi Osaka clinched her fourth Grand Slam title on Saturday after beating Jennifer Brady at the Australian Open. Here's how her two US Opens and two Australian Opens were won:
"For sure he has more experience, but more things to lose," Medvedev said about his final opponent Novak Djokovic.
Australian Open 2021: Aslan Karatsev fairytale has happy ending as qualifier takes home points, confidence, and prize money
Qualifier Aslan Karatsev, who had never before qualified for a Grand Slam, will soar from 114 to 42 in the rankings and collects $658,000 in prize money, more than doubling his career earnings.
After beating qualifier Aslan Karatsev, Djokovic, showing no ill-effects from an abdomen injury sustained in the third round, said, "This is the best I've felt in the entire tournament. I could swing through the ball. No pain. The best match so far."
"I wasn't thinking about a lot of things," said Tsitsipas. "How would I describe myself? Nirvana. Just was there... playing, not thinking."
"I'm not the guy that's going to find excuses on that or going to complain about what happened, no. Just accept. I never considered myself an unlucky person at all," Rafael Nadal said after his ouster.
In Australia, Ankita Raina got her much-awaited Grand Slam debut and in the same week a first WTA Tour level win.
Australian Open 2021: For some, facing a Grand Slam legend means a dream come true. And a lopsided defeat
It is a tricky balance when someone of Cameron Norrie’s ilk — ranked 69th and, until this week, the owner of a grand total of six wins in Grand Slam matches — goes up against someone of Rafa Nadal’s stature on one of their sport’s biggest stages.
Australian Open 2021: Rafael Nadal emerges unscathed from 'tough' workout to keep Grand Slam dream alive
World No 2 Rafael Nadal accelerated his pursuit of a record 21st Grand Slam title on Saturday with a testing victory over Cameron Norrie.
World No 1 Ashleigh Barty said it was "very strange" to play behind closed doors, a day after more than 22,000 fans visited Melbourne Park, as the five-day, state-wide lockdown went into force.
Australian Open 2021: 'Feel like I played better', teenager Coco Gauff unruffled by second-round defeat
Gauff showed plenty of promise but fell to fifth seed Elina Svitolina 6-4, 6-3 in a free-wheeling second-round contest on Rod Laver Arena.