The pair face a stern challenge from youthful force Alexander Zverev, looking for a first major as the torch-bearer for the next generation.
But there are question marks over the fitness of Rafael Nadal and Andy Murray, meaning it remains to be seen if all members of the “Big Four” will again prove a force to be reckoned with.
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.
It put him on a par with other six-time Australian Open winners Djokovic and Roy Emerson – but the Australian great's victories all came before the Open era.
By contrast, the 31-year-old Djokovic endured a miserable early Melbourne exit, followed by elbow surgery and a string of disappointing results that saw him drop outside the top 20.
But since winning a fourth Wimbledon in July the Serb rose inexorably back to number one by losing only three further matches — one of which was to Zverev at the ATP Finals.
World Number 1 Novak Djokovic in Melbourne on Monday. Photo: AFP
Djokovic won his third US Open in September to put him on 14 Grand Slams — three behind Nadal and six behind Federer.
Ageless Swiss master Federer, now 37, will remain a chief threat to the Serb but the other two members of the Big Four look to be struggling after an injury-plagued 2018.
Second-ranked Nadal, 32, pulled out of his Brisbane warm-up tournament with a thigh strain although he returned for an exhibition in Sydney and insisted he was healthy.
Murray, 31, looked way below his best in a second-round straight-sets Brisbane defeat to Daniil Medvedev.
NextGen 'already there'
“I think if we are healthy and playing well, the four guys still have probably the best chance to always win Slams,” said Djokovic.
The Serb warned however that “the next generation is already there” and picked young guns Zverev of Germany, Borna Coric of Croatia, Karen Khachanov of Russia and Greece's Stefano Tsitsipas as key threats to the Big Four, who have won a staggering 49 of the last 56 Grand Slams stretching back to 2004.
“It's just a matter of time when we will see some of them competing in the last stages of Grand Slams,” said Djokovic.
Zverev, 21, starts the Australian Open full of confidence after an impressive warm-up in Perth's mixed teams Hopman Cup, despite his terrible record at Grand Slams.
Germany's Alexander Zverev has been tipped to be one of the key threats to the Big Four of men's tennis. Photo: AFP
The German has never got beyond the third round in Melbourne.
Last year, seeded four, he crashed out in the last 32 to South Korea's Chung Hyeon and has only reached one quarter-final in his 14 major appearances.
Federer seems to thrive at the start of the year and begins his campaign on the back of winning the Hopman Cup. He is hunting a third successive Australian Open after last year becoming the oldest world number one in the 45-year history of the ATP rankings.
Competitive at 37
“(Pete) Sampras once upon a time said, 'If you win a Slam, it's a good season',” said Federer, now ranked three, who skipped Roland Garros and had disappointing exits at Wimbledon and the US Open.
“I played super well in Australia again. So obviously I can't wait to go back there. I'm very proud that at 37 I'm still so competitive.”
Murray's hip surgery meant he played just six events in 2018, and Nadal's truncated 2018 campaign was bookended by injuries that forced to him to retire in both the Australian and US Opens.
But the Spanish king of clay still managed to win five titles including a record-extending 11th French Open.
World number five Argentine Juan Martin del Potro, beaten by Djokovic in the US Open final, will miss Melbourne after fracturing his patella in Shanghai in October.
And Cilic, who pushed Federer all the way in the final last year, heads into the tournament after pulling out of a warm-up event in India last week with an injured knee.
Home fans will look to Alex de Minaur and Nick Kyrgios, but the latter is searching for form after a troubled 2018 and tumbled out of the Brisbane warm-up, where he was defending champion, in the second round.