Amanda Anisimova, a 20-year-old American ranked 60th in the world, ensured that so-called final-before-the-final wouldn't happen when she beat the four-time major champion 4-6, 6-3, 7-6 (5) Friday.
"I knew I had to be playing sharp if I wanted to give myself a chance," said Anisimova, who took out Olympic champion Belinda Bencic in the second round and then accounted for the 2021 Australian Open champion.
After losing the first set, Anisimova knew she needed to get more aggressive or she would be out of the tournament.
Anisimova saved two match points in the third set, serving to stay in the match, and ended it with an ace. She hit 46 winners to Osaka's 21.
It's the fourth time Osaka has been unable to defend a major title, and the 11th time in a Grand Slam she has been knocked out in the third round, including last year's US Open.
After winning the title last year -- her second at Melbourne Park in three years -- Osaka withdrew from the French Open in the second round and skipped Wimbledon as she took a break for her mental health. After an early loss at the US Open, she took an extended layoff to reset and arrived at the year's first major with a seeding of No. 13.
Barty advanced with a 6-2, 6-3 win over 30th-seeded Camila Giorgi on Rod Laver Arena, the match starting later and finishing earlier than the Osaka-Anisimova contest on the adjoining Margaret Court Arena.
Barty has conceded only eight games and spent less than three hours on court in the first three rounds at Melbourne Park. The Wimbledon champion and 2019 French Open winner is aiming to be the first Australian woman to win her home championship since Christine O'Neil in 1978.
Two-time Australian Open champion Victoria Azarenka overpowered 15th-seeded Elina Svitolina 6-0, 6-2 to reach the fourth round at Melbourne Park for the first time since 2016.
Before she had a chance to analyze both players she might meet next, a question was posed to her son about the two-time Australian Open champion's third-round performance.
Five-year-old Leo, wearing his sunglasses in the news conference room and sitting on his mother's knee, responded succinctly: "Awesome!"
Azarenka thanked her son, then listed the positive points from her perspective. Those included: "The amount of aggressivity I could bring point after point, applying a lot of pressure, the consistency. Taking control of my end of the court."
Since a quarterfinal run in Australia in 2016, Azarenka lost first-round matches last year and in 2019, and missed the hard-court tournament in 2017, 2018 and 2020.
The 32-year-old former No. 1 from Belarus is feeling comfortable, fulfilling the dual roles of player and mother in Melbourne.
"I always feel privileged that I'm able to have him here," Azarenka said. "These kind of moments are really priceless for me. To be able for me to share that with my son is pretty incredible."
Fourth-round pairings that were set up Friday include fifth-seeded Maria Sakkari against 21st-seeded Jessica Pegula and No. 8 Paula Badosa against Madison Keys, who held off Wang Qiang 4-6, 6-3, 7-6 (2) on Friday.