Williams has been unstoppable in New York but faces her toughest test yet when she battles Czech Pliskova.
Williams is seeking her first Grand Slam title since becoming a mother last September.
But eighth seed Pliskova, a former world number one and US Open finalist in 2016, presents a tough task for the 36-year-old.
Williams though is still determined to get back to her best as she aims to win a record-equalling 24th Grand Slam title in New York.
“That desire has not gone down at all,” she said.
“And I don’t think it was capable of going up, because if it was at a 10, I was at a 15 or a 20 – and I’m still there.”
Pliskova reached the US Open final two years ago, beating Williams in the semi-finals.
She has never won a Grand Slam but is looking forward to taking on arguably the best female tennis player of all time.
“It’s the match you want to play,” Pliskova said of Williams.
“If I’m this far, I want to be in Arthur Ashe, playing Serena. I remember that feeling.
“It doesn’t have to be that I beat her, but just to be there and play against her.
“I know she’s not No 1 now as she was two years ago, but she’s still an amazing player. It would be so much better to play her.”
Serena Williams vs Karolina Pliskova LIVE
Serena Williams 6-4 5-3 Karolina Pliskova
Pliskova holds and, after almost an hour and a half of action, Williams will serve for the match.
Serena Williams 6-4 5-2 Karolina Pliskova
Pliskova had three break points to get the second set back on serve but Williams shows her power and is now just one game from victory. And she lets out a huge roar to show just how important that hold was.
Serena Williams 6-4 4-1 Karolina Pliskova
Interesting. Pliskova breaks back and stops the rot in the process. Is this the start of a comeback?
Serena Williams 6-4 4-0 Karolina Pliskova
Serena is walking away with this now. Another break and the American is just two games away from a semi-final spot.
Serena Williams 6-4 2-0 Karolina Pliskova
That’s six games in a row as Williams gets the early break in set two
Serena Williams 6-4 Karolina Pliskova
Four games in a row for Williams and that’s the first set. She holds comfortably before breaking Pliskova again following a long battle.
Serena Williams 4-4 Karolina Pliskova
Now it’s Williams’ turn to have a comfortable service game before she gets the break and gets back into this first set. This quarter-final is not disappointing.
Serena Williams 2-4 Karolina Pliskova
Williams gets herself two break points at 15-14 but Pliskova reels off four points in a row for a big hold.
Serena Williams 2-3 Karolina Pliskova
Eighth seed Pliskova holds comfortably again and then has more break points. Far too many unforced errors from Williams at the moment. But the American holds on, somehow.
Serena Williams 1-2 Karolina Pliskova
Pliskova holds comfortably and then has 15-30 on Williams’ serve. A couple of big serves gets the American game point but Pliskova takes it to deuce. And Pliskova finally converts her third break point!
Serena Williams 1-0 Karolina Pliskova
And Williams gets on the board straight away. A couple of big serves has her on her way, though Pliskova did pounce on one second serve.
00.18: It’s 17th seed Williams to serve first in New York… GAME ON!
00.10: Serena Williams and Karolina Pliskova are now on Arthur Ashe and just warming up. Moments away from this tantalising quarter-final clash.
23.55: It’s not long now until the night session begins at the US Open. Will Williams advance to the semi-finals?
23.40: Williams and Pliskova have faced each other twice before with each winning one. Williams won at Stanford in 2014 before Pliskova got her revenge in the US Open semi-finals in 2016.
23.30: Serena Williams vs Karolina Pliskova is the first night match on Arthur Ashe with the clash expected to begin shortly after midnight.