World number one Djokovic was broken five times by the Briton in their last-16 clash and suffered his first loss of the year, having won the Australian Open for the ninth time in February.
Thirteen aces among her 36 winners helped Osaka overcome a slew of unforced errors of her own and set up a third-round meeting with Serbian qualifier Nina Stojanovic, who surprised Yulia Putintseva
Medvedev finished runner-up at a Grand Slam for the second time as he was swept aside by top-ranked Novak Djokovic in Sunday's final in Melbourne, the Serb collecting his 18th major title.
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.
Karatsev was also the lowest-ranked man, at 114, to make the semis at a Slam since Goran Ivanisevic at Wimbledon in 2001 when ranked 125.
Australian Open 2021: Novak Djokovic beats Alexander Zverev, into ninth semi-final; Serena Williams sets up Naomi Osaka last-four clash
Djokovic pulled himself together and pulled out the victory, reaching his ninth semi-final at Melbourne Park by eliminating No 6 seed Zverev 6-7 (6), 6-2, 6-4, 7-6 (6)
Australian Open 2021: Serena Williams against Simona Halep, Naomi Osaka versus Hsieh Su-wei in quarter-finals
Williams leads the series 9-2, but Halep won their most recent showdown, 6-2, 6-2 in the 2019 Wimbledon final.
Karatsev, ranked 114, is the first Grand Slam debutant to reach the quarter-finals at a major since Romanian Alex Radulescu at Wimbledon in 1996 and only the seventh in the Open era.
Australian Open 2021: Dominic Thiem stunned by Grigor Dimitrov; Serena Williams, Naomi Osaka survive
A fatigued-looking Thiem, coming off a five-set win over Australia's Nick Kyrgios, slumped in straight sets to Bulgaria's Grigor Dimitrov who took it 6-4, 6-4, 6-0 in just over two hours.
Russia's Andrey Rublev needed just eight minutes to reach the Vienna ATP quarter-finals on Thursday when Italian teenage opponent Jannik Sinner was forced to quit.
French Open 2020: Novak Djokovic breezes into quarters; Stefanos Tsitsipas overcomes eye problem to win
"I had a problem with my eye so that's why I had to call the doctor. It happened in my earlier matches too. It's still red and irritated," Tsitsipas explained.
French Open 2020: Novak Djokovic into last-16 with ease as Daniel Altmaier strikes new blow for underdogs
World number one Djokovic swept past 153rd-ranked Galan 6-0, 6-3, 6-2, his most challenging moment coming when he helped ground staff lay more clay on the surface of Court Philippe Chatrier after rain had made it treacherous
Italian Open 2020: Simona Halep extends winning streak to 11 matches; Novak Djokovic beats Filip Krajinovic
Halep, who is actually on an 11-0 run overall stretching back to February, recovered an early break in the opening set and then overpowered her 29th-ranked opponent the rest of the way.
Western & Southern Open: Ailing Djokovic beats Berankis to reach round of 16; Serena claws out victory
Novak Djokovic battled through neck pain on the way to a 7-6 (7/2), 6-4 victory over Ricardas Berankis at the Western & Southern Open, where second seed Dominic Thiem crashed out.
Former Wimbledon and US Open champion Murray was given slot alongside Americans Tommy Paul, Tennys Sandgren and Frances Tiafoe for the event, a warm-up for the Grand Slam in New York which begins on 31 August
Novak Djokovic's Adria Tour event lacked bit of common sense, says former ATP players' council head Vijay Amritraj
Djokovic has apologised and admitted it was probably “too soon” to run the event, which was played in front of packed stands in Belgrade.
'Protocols are in place for reason', Wimbledon chief expresses disappointment over botched Adria Tour
Wimbledon chief said, 'The images were disappointing and I think that ... what needs to come out of it is everybody involved — not just players, but administrators, organisers, entourages — understands that the protocols, rules and regulations are in place for a reason.'
Novak Djokovic goes from aiding lower ranked players to endangering countless in miserably quick fall as role model
Djokovic is not being berated for failing to live up to the lofty expectations that come with the territory of being an all-time great; he is being slammed because he behaved like a stupid, selfish jerk.
Djokovic tested positive on Tuesday after taking part in a tennis exhibition series he organised in Serbia and Croatia, becoming the fourth player to test positive for COVID-19.
After Grigor Dimitrov, Borna Coric, Viktor Troicki test positive for COVID-19 having played in Adria Tour exhibition event
Borna Coric and Viktor Troicki tested positive for COVID-19 after playing in Novak Djokovic’s Adria Tour exhibition event, raising serious concerns for tennis governing bodies in their bid to restart the sport after a lengthy shutdown.