Williams had pull out of the Hopman Cup with a knee injury a fortnight ago and the problem looked to be lingering when she was pictured taking treatment in practice last week.
The American, however, showed few signs of weakness as she dispatched Taiwan’s Hsieh Su-wei 6-1 6-2 in the Rod Laver Arena, hitting 26 winners and wrapping up victory in just one hour.
Russia’s Daria Kasatkina now waits in the third round and Williams said she feels fit and raring to go.
“No it (her knee) hasn’t been bothering me in a long time. So it’s been okay. It’s totally fine,” Williams said.
“I don’t think I made that many errors today. Something I was hopefully trying to get back into.
“And I moved much better today I think, so slowly but surely feeling a little bit better.”
Williams has never faced Kasatkina in a competitive match before, but she might do well to glean some tips from her sister Venus, who lost to the 18-year-old world number 69 in Auckland earlier this month.
“I don’t think it’s going to be easy,” Serena said.
“Any time someone is beating Venus they are more than likely playing really good. So I definitely will be ready for that.
“I obviously will ask Venus what she thought of the match, and I’m sure (coach) Patrick (Mouratoglou) will know everything about her match. He’s really good at studying.”
Sharapova, seeded fifth in Melbourne, is due to meet Williams as early as the quarter-finals and the Russian was ruthless in beating Aliaksandra Sasnovich of Belarus 6-2 6-1.
Injury problems have hampered Sharapova for the best part of a year and she was forced to withdraw from the Brisbane International with a pain in her left forearm two weeks ago.
“I feel pretty good,” said Sharapova, who will American Lauren Davis in round three.
“I felt I was more confident with my left hand today. Especially when it’s in the hand and wrist area, it’s in the back of your mind even though you’re feeling it. I felt really good and confident today about it.”
The biggest shock came in Margaret Court Arena, where sixth seed and two-time Wimbledon champion Petra Kvitova was knocked out by Australian Daria Gavrilova.
Gavrilova, who was born in Moscow but switched nationality last year, beat the Czech 6-4 6-4 to book a third round match-up with world number 28 Kristina Mladenovic.
“Coming into this match I was pretty confident that I could beat Petra,” Gavrilova said.
“I knew that she didn’t have enough matches before. She didn’t even play anything before the Oz Open. So I thought it was a good chance.”
In the men’s, Roger Federer cruised into the third round with a 6-3 7-5 6-1 victory over Ukraine’s Alexandr Dolgopolov.
Federer was rarely troubled by Dolgopolov, hitting 39 winners and wrapping up victory in just an hour and 33 minutes.
The result sets up an intriguing third-round clash with Bulgarian Grigor Dimitrov, who was once considered a potential successor to Federer’s dominance but has struggled to fulfil his potential.
“I think it’s a tough draw,” Federer said. “He’s got the game to be really dangerous. He’s fit enough for a five-setter so I’ve definitely got to bring my best game to the court on Friday.”
Top seed Novak Djokovic and Japan’s Kei Nishikori also moved safely through, as did Czech sixth seed Tomas Berdych, who will face Australian Nick Kyrgios in round three.
Kyrgios beat Uruguay’s Pablo Cuevas in straight sets but fumed for the first half of the match about being given the wrong shorts.
The 20-year-old finally changed to a new black pair in the second set and seemed far more comfortable from then on.
“Just a bit of a mix-up before the game. I guess it will be fixed by the next round,” Kyrgios said.
Asked what he was looking for from his team, Kyrgios added: “Some new shorts, I guess. And I got some.”