She has said she will not hesitate to ask eight-time Australian Open victor Novak Djokovic for a word of advice about defending major titles but feels her performances previous year give her "some air to breathe" when it comes to expectations.
Australia has always been a happy place for Williams with seven of her 23 major titles coming at Melbourne Park, including her last in 2017 when she beat sister Venus in the final and later announced she was pregnant.
She had broken the Brit's self assurance and went on in the deciding set to claim victory with her consistency and power to win the match 3-6, 6-3, 6-1.
Reigning Australian Open champion Sofia Kenin, who was 7-5 up when Camila Giorgi retired from their match, is also through.
There were 89 matches scheduled at the Australian Open site on the middle day of a compressed week of six tournaments - including three WTA events and three for the men's tour.
That injury kept Williams out of competitive tennis until last week.
Resetting, Osaka found her range on serve, applied more spin to her shots and began dictating the direction of rallies with her forehand.
The 22-year-old Kenin revealed her superstitions would require an adjustment on the dining front this time round.
Osaka plays Katie Boulter in the next round after the British woman knocked out teenage sensation Coco Gauff 3-6, 7-5, 6-2 in one hour and 43 minutes.
Ash Barty has showcased her fighting qualities in another pre-Australian Open victory at Melbourne Park.
Home favourite Barty, who is hoping to break Australia's 43-year singles title drought at the Open, had a fright in her Yarra Valley match against Marie Bouzkova of the Czech Republic, but recovered to win 6-0, 4-6, 6-3.
"It's the first time I'm experiencing coming back to a Grand Slam where I have to - not have to, where I want to try to defend my title". That, in turn, pushed the Australian Open back three weeks from its usual start.
"Honestly I like playing long matches, just because I can gauge the condition of the court and I feel my fitness gets better", Osaka said.
Barty will face Shelby Rogers, a 7-6 (1), 6-3 victor against No. 7 seed Petra Martic of Croatia.
At the All-England Club in 2018 she was dismissed 6-3 6-3 by Angelique Kerber and a year later humbled 6-2 6-2 by Simona Halep.
Things got more complicated later Wednesday, when the state government announced that a worker at one of the tournament's three Melbourne quarantine hotels had tested positive for COVID-19. Two-time Australian Open champion Victoria Azarenka had a first-round bye.