Serena Williams won her 23rd major Down Under two years ago while two months pregnant.
Naomi Osaka's win equals her best performance at the Australian Open, where she reached the last 16 in 2018 but lost to Simona Halep.
The pressure on the reigning French Open champion will only increase in her next round.
The Russian five-time Grand Slam champion was forced to stay up late in her second-round match.
Simona Halep had to dig deep for a come-from-behind win against Kaia Kanepi in the first round of the Australian Open.
Serena Williams won her 23rd title and seventh at Melbourne Park while eight weeks pregnant two years ago.
Serena Williams is gunning to match Margaret Court's record of singles majors and claim an eighth Australian Open crown.
Simona Halep takes the top seeding among the women courtesy of her world number one ranking.
Nadal dominated the singles charts with 7,660 points, and Halep remained No. 1 in the WTA rankings despite being down with a back injury.
Simona Halep had pulled out of last month's China Open and withdrew from this week's Kremlin Cup because of the persistent problem.
Simona Halep played two Grand Slam finals winning the French Open crown and won titles in Shenzhen and Montreal.
Roger Federer remains behind Nadal with 6,900 points. And in the WTA rankings, Japan's Naomi Osaka jumped two positions to the fourth spot.
Simona Halep said that she was "worried now" after a persistent back problem forced her out of the China Open after just 31 miserable minutes.
The French Open champion suffered a back injury during a practice session on Sunday and failed to fully recover for her opening match in Wuhan.
Romania's Simona Halep continued to lead Women's Tennis Association (WTA) rankings released on Monday, ahead of Denmark's Caroline Wozniacki.
Williams can match Margaret Court's all-time record of 24 majors with another title at Flushing Meadows.
It was a second straight first-round exit at Flushing Meadows for Romania's Simona Halep, who dropped her opening match to Maria Sharapova last year.
Kiki Bertens defeated the world number one Simona Halep 2-6, 7-6 (8/6), 6-2 in the Cincinnati WTA final.
