Clijsters spent two years away from competitive tennis
Kim Clijsters continued her return to competitive tennis with victory over Svetlana Kuznetsova, as the Williams sisters were beaten in Cincinnati.
The Belgian, 26, is playing her first event after a two-year break during which she gave birth to a daughter.
And Clijsters was more than a match for sixth seed Kuznetsova, winning 6-4 4-6 6-2 in sweltering conditions.
Venus Williams went down 7-6 (7-2) 6-4 to Flavia Pennetta, and Sybille Bammer beat Serena Williams 7-5 6-4.
Pennetta's superb run continued as she beat third seed Venus for her 14th consecutive victory, having won back-to-back titles in Palermo and Los Angeles.
Venus made 38 unforced errors as 14th seed Pennetta outplayed the American to clinch her fourth victory in their seven meetings.
"I have to give her credit for playing well and keeping the ball in play," said Venus. "I just made too many errors.
It's better than I expected. I'm very happy I have been able to stay focused
"After a while it was obvious that she was just keeping the ball in play and waiting for me to self-destruct. I kept pressing that red button today and it didn't work out."
Second seed Serena Williams, who has complained of feeling unwell this week, played a poor match and was given a code violation for racquet abuse on her way to a limp defeat against Bammer.
The Austrian will next play Serb Jelena Jankovic, with the fifth seed beating Belarus star Victoria Azarenka 7-5 7-6 (7-4).
Serena said: "I never played worse in my life. It was really a bad match. I just couldn't get it together."
Italian Pennetta set up a clash with Daniela Hantuchova, who defeated Vera Zvonareva 7-6 (8-6) 0-6 7-6 (7-5).
Clijsters will now face a mouthwatering clash with world number one Dinara Safina, who cruised past China's Peng Shuai 6-3 6-4.
"She's a great player," Safina said of Clijsters. "I think for sure she plays exactly how she did. You cannot lose your talent. You cannot lose anything.
"If you are a great player, it doesn't matter. Give (Pete) Sampras a racket now and he will play exactly the same. Maybe she will be a little bit slower, but she's still young."
The Belgian was magnificent from the baseline in the opening stages against Kuznetsova and looked set for a comfortable win at a set and 3-0 up.
But Kuznetsova pegged her back and saved two break points at 4-3 down, the second with a Hawkeye challenge, before getting a break of her own in the following game with another desperately close challenge.
The Russian served out the set before the players took a 10-minute break ahead of the final set as the heat rule was invoked.
And the brief rest allowed Clijsters to regroup and wrestle the momentum away from the French Open champion with an early break in the decider as she powered to a stunning win.
"It's better than I expected," said the Belgian. "I'm very happy I have been able to stay focused.
"I was hitting the ball well on my groundstrokes but my serve was not going so well and she started to get the hang of it in the second set.
"But I made some adjustments and luckily I was able to come through."
Fourth seed Elena Dementieva eased past Romania's Sorana-Mihaela Cirstea 6-4 6-4, and the Russian will next play eighth seed Caroline Wozniacki who advanced when Hungary's Melinda Czink retired because of injury in the first set.