In the women's draw, Caroline Wozniacki and Elina Svitolina will look to continue their progress towards a likely semi-final match-up.
Sharapova, the Melbourne Park champion here 10 years ago, was sent packing in just 64 minutes as a resurgent 21st seed dismantled her 6-1, 6-3.
Sharapova should be concerned.
"That, to me, is a big thing because I'll be back on the practice court; I'm not starting from zero".
It's another thing to be completely crushed, which was the case with Sharapova. Maria Sharapova of Russian Federation hits a shot against Angelique Kerber of Germany. "But I'm here because I'm motivated to get better at my craft". Above all, he is Federer, having reinvented himself at 36 like no other player in the history of the game surely could have done.
It is no secret that Serena Williams and Sharapova are not the best of friends.
Twice in his first three service games Djokovic had to save break points, but after taking a 3-2 lead he never looked back and he reeled off the next three games to take the first set, his backhand and touch at the net showing promising signs.
Twelve-time Grand Slam Champion Novak Djokovic advanced into the pre-quarters of the Australian Open despite an injury scare here on Saturday.
The result left Kerber as the only remaining Grand Slam victor in the women's draw, with the loss Friday of French Open champion Jelena Ostapenko.
Federer entered the Australian Open past year under similar circumstances, coming off an extended break for a knee injury, and went on to win the title.
The German endured a nightmare 2017 after winning the Australian Open and US Open titles in 2016 and climbing to world number one but is unbeaten so far this year after winning the warm-up event in Sydney.
Sharapova made her tournament comeback after serving a 15-month doping ban after a positive test for a banned substance here in 2016.
The Japanese 20-year-old's win finally marked some success in the third round at a major - she was previously 0 for 5. Sharapova's opponent Saturday, Kerber, is also 30. "I'm very happy that I was able to rise to a level that I needed to beat Richard", he said.
"I worked hard on the court".
And you can't blame her struggles on being banged up, because everyone's dealing with varying degrees of aches and pains.
Djokovic, who was upset by Denis Istomin in the second round of last year's tournament, was workmanlike as he broke the Spaniard's serve five times, although his errors outnumbered his winners 40-37.
And Sharapova is still in search of her championship form.
The match was originally scheduled for Rod Laver Arena, but was moved to Margaret Court Arena due to a backlog of long matches at the larger venue.
Roger Federer and Novak Djokovic look destined to collide for the 46th time before they leave Melbourne, where they own a total of 11 titles.
"There's a lot of things I need to improve on". "Today was not enough (but). looking at the overall picture, there's a lot to build from".