In men's action Wednesday, No. 28 Lucas Pouille of France reached his first Grand Slam semifinal by beating 2016 Wimbledon runner-up Milos Raonic of Canada 7-6 (4), 6-3, 6-7 (2), 6-4. Pouille, who is coached by two-time major champion Amelie Mauresmo, had been 0-5 for his career at the Australian Open until last week. His next opponent will be 14-time major champion Novak Djokovic, who moved on when 2014 U.S. Open finalist Kei Nishikori stopped playing while trailing 6-1, 4-1.

Nishikori was treated for leg problems by a trainer.

Williams' surprising departure scuttled what would have been a much-anticipated rematch against Osaka, who beat her in the chaotic U.S. Open final last September.

This defeat is the earliest in Australia for Williams since 2014, when she exited with a fourth-round loss to Ana Ivanovic. Since then? She won the tournament in 2015, lost in the final in 2016, and won again in 2017 while pregnant, before missing last year's edition a few months after the birth of her daughter.

As for chasing Margaret Court's all-time mark of 24 Slam trophies in singles, Williams said: "It hasn't happened yet, but I feel like it's going to happen."

The match against Pliskova was played under a stifling sun, with the temperature around 80 degrees (25 degrees Celsius). Williams — coming off an intense three-set victory over No. 1 Simona Halep in the fourth round — often stepped into the patches of shade behind each baseline.

She did not start well, not well at all. Her mistakes were mounting and deficit was growing.

In the first set alone, Williams made more than twice as many unforced errors as her opponent, 11-5, a pattern that would continue throughout. By the end, the margin was 37-15.

Looking increasingly frustrated, Williams would yell at herself after mistakes or gesture as if to say, "That's NOT how I should be hitting the ball!" Add it all up, and Pliskova led by a set and a break at 3-2 in the second.