Williams -- the No. 17 seed -- swept No. 8 Pliskova 6-4, 6-3 on Tuesday night at Arthur Ashe Stadium at the USTA Billie Jean King National Tennis Center. Fellow American -- and No. 3 seed -- Sloane Stephens was booted from the tournament in straight sets by No. 19 Anastasija Sevastova 6-2, 6-3.
The 23-time Grand Slam champion fell behind 2-1 in the first set, before storming back for the victory.
"I just thought that I wasn't playing my best tennis," Williams told reporters. "I was thinking that I can play better so that was the good news. I thought I should try to make less errors. At that point i was missing a lot of shots I just had to figure out a way to at least make one and one at a time."
Williams needed 1:26 to dispatch of Pliskova, while Sevastova beat Stephens in 1:24. Williams had 13 aces in her victory, compared to Pliskova's three first-chance winners.
"I've been a couple of steps away at the last Grand Slam so I'm definitely not ahead of myself," Williams said. "I still know that no matter if I'm in the semifinals or in the finals, I have a really long way to go to win that. That proved to be true at Wimbledon so I'm just taking it one at a time, literally."
No. 1 Rafael Nadal remains the top overall seed in the tournament. He outlasted No. 9 Dominic Thiem in a five set thriller at Arthur Ashe Stadium to also clinch a spot in the semifinals. Thiem took the initial lead in the 4:49 match, winning the first set 6-0. Nadal won the next two sets 6-4, 7-5 before Thiem claimed the fourth set and Nadal closed out the Austrian in the fifth set.
No. 3 Juan Martin del Porto ousted No. 11 John Isner in four sets to reach the semifinals. No. 6 Novak Djokovic takes on John Millman at 8:15 p.m. Wednesday for a chance to reach the semifinals. No. 7 Marin Cilic battles No. 21 Kei Nishikori in search of the same feat.
Nadal and del Porto face off in a semifinal matchup on Friday in New York. On the women's side, No. 20 Naomi Osaka battles Lesia Tsurenko at noon on Wednesday in another quarterfinal clash. No. 14 Madison Keys takes on No. 30 Carla Suarez Navarro in an evening quarterfinal tilt.
Williams and Sevastova face off at 7 p.m. on Thursday with a trip to the 2018 U.S. Open final on the line. The six-time U.S. Open champ has never faced the Latvian.