This time, the American legend outgunned the World Number one, Osaka 6-3, 6-4 and Serena reached her first-ever non-Slam semifinal since the Rome event in 2016.
That set the stage for Williams, a 37-year-old American who will try for a record-tying 24th Grand Slam singles title at the upcoming US Open, to again face Osaka after the controversial finish to their Grand Slam showdown last year in NY.
Japanese star Naomi Osaka will reclaim the WTA world No.1 spot for the second time in her career when the new rankings are made official next Monday.
Asked about Osaka dubbing her "Tennis Mum" in her on-court interview, Williams said: "I would say more like 'tennis grandmum.' It was very kind of her to say mom".
"We haven't played since NY which was a really good match for her and I just wanted to come out and win a set this time because she's beaten me twice", the 37-year-old joked.
Williams had slow starts in her previous two outings this week but came out much stronger for this one and delivered a serving masterclass that denied Osaka any break point opportunities.
"And today I felt it more, so that's why I chose to retire", said Halep, no doubt exercising extra caution with the final Grand Slam of the year due to start on August 26.
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Bouzkova notched her third straight win over a Grand Slam champion, having beaten former US Open victor Sloane Stephens and former French Open champ Jelena Ostapenko.
She broke Bouzkova in the next game to finally take control and end the Czech's breakout week. "I just went out there and I never gave up because it's not over until it's over".
The new Naomi Osaka isn't going to let a loss get her down.
"But, yeah, I'm not really mad at this".
"In the third set I told myself, 'Go big or go home, ' " Andreescu said. She added: "But there were chances where she hit shorter balls, but I wasn't expecting her to, so I didn't move up in time". I know her game. Beating the world's No. 1 player on Friday is pretty good sign that she is ready to go.
Osaka's form fell off a cliff after taking number one with the Australian Open title and she later conceded the pressure had been tough to handle.
Pliskova eliminated Estonia's Anett Kontaveit 6-3, 7-5 to set up a last-eight clash with rising Canadian star Bianca Andreescu, who outlasted fifth-seeded Dutchwoman Kiki Bertens 6-1, 6-7 (7/9), 6-4.
Williams will face Czech qualifier Marie Bouzkova on Saturday.