Hard-hitting Czech Karolina Pliskova toppled two-time champion Venus Williams 4-6, 6-4, 7-6 (7/3) on Monday to reach her first Grand Slam quarter-final at the US Open.

Pliskova, who had never before made it past the third round of a major in 17 prior attempts, saved a match point en route to a victory which scuppered a possible semi-final clash between Williams and her sister Serena.

The 36-year-old Williams was vying to become the oldest woman to reach the US Open quarters in the Open Era.

But the in-form Czech -- who shocked world number two Angelique Kerber in the final at Cincinnati in August -- settled her own late nerves to pull off the upset in front of a partisan Arthur Ashe stadium crowd.

"I was prepared that I'm going to play Venus, it's going to be tough because people will be cheering for her," Pliskova said.

Williams was philosophical about her failure to convert a match point against Pliskova's serve in the 10th game of the third.

"She had a great serve," Williams said. "She hit another great shot and I still played a great defensive shot. I did the best I could on that.

"Whenever you have a match point on someone else's serve, it's a little bit of an asterisk. I really have no regrets on that."

Pliskova then broke Williams for a 6-5 lead -- with the help of a favorable net cord bounce.

Serving for the match and up 40-0, however, Pliskova couldn't close it out. A double fault followed by four strong points from Williams sent it to the tiebreaker.

"To be honest it was very difficult after I lost my serve for six-all," Pliskova admitted. "She played a very good game."

There was one last agonizing moment for Pliskova, who appeared to have won the decider with a ball that was ruled out on a challenge.

But she was able to celebrate for real when Williams sent a service return long on the next point.