- Tag results for Novak Djokovic
Tiafoe -- who at the age of 20 had already caused the shock of the first round in stunning fifth seed Kevin Anderson -- registered a second notable scalp on his 21st birthday.
The Serb angrily blamed floodlights for dropping a tournament set for the first time as he beat Denis Shapovalov 6-3, 6-4, 4-6, 6-0 in the third round.
On day six at Melbourne Park, the Romanian finally hit form to pull off her best win of the year and cruise past the veteran American 6-2, 6-3.
Djokovic, the 14-time Grand Slam winner, in Melbourne for the Australian Open, is Serbia's best-known sportsman and perhaps the nation's most-famous person.
The top seed vanquished his old French foe for the 17th time in 27 tour meetings stretching back 11 years and advances to face Canada's 25th seed Denis Shapovalov in the third round.
Djokovic won the decider for his maiden major title but it doesn't detract from Tsonga's memories.
But Murray dropped a pre-Grand Slam bombshell, breaking down during a tear-filled press conference as he revealed chronic hip pain means he will retire after Wimbledon -- if he can carry on that long.
With world number five Juan Martin del Potro missing through injury, South Africa's Kevin Anderson is elevated to fifth seed with last year's beaten finalist Marin Cilic at six.
Twelve months ago Federer rolled back the years once more at the Rod Laver Arena to beat Marin Cilic in five pulsating sets and lift an emotional 20th Grand Slam.
Roger Federer used the Hopman Cup as his launching pad for winning the past two Australian Opens.
The Serb fell to his first defeat of the season in a high-quality contest lasting more than two-and-a-half hours.
The 31-year-old Djokovic is currently six majors behind Federer and three adrift of Rafael Nadal, but is likely to keep up the pressure on his rivals this upcoming season.
With the veterans in no hurry to step out of the limelight, 2019 could again see Djokovic and Nadal -- and perhaps even Federer -- dominating the circuit and extending their rivalry.
The 31-year-old started his year with a miserable early exit at the Australian Open, followed by elbow surgery and a string of disappointing results on his return to the court.
The Serbian world number one looked unbeatable heading into Sunday's final, winning all four of his matches in London in straight sets and not dropping serve once.