(CNN) -- Entering this season Petra Kvitova had reached the quarterfinals at every grand slam except for the U.S. Open.
She memorably won Wimbledon in 2011 to open her account at majors, sweeping past Maria Sharapova in the final, and achieved semifinals at the Australian Open and French Open last year.
Her drought, however, in New York persists after the Czech managed just three games in the third round against little-known American Alison Riske and exited 6-3 6-0.
The outcome was better for another Wimbledon champion, Rafael Nadal, who cruised in straight sets against Ivan Dodig.
Kvitova has found it difficult playing in hot and humid conditions in the U.S. in the past because she suffers from asthma and this week the lefty revealed she had been battling a virus and fever.
Following a close first set, Kvitova claimed a mere 15 points in the second.
"My body wouldn't let me fight," Kvitova told reporters.
Riske, ranked at a career-best 81st, reached the fourth round at a grand slam for the first time, much to the delight of her home crowd.
Her best results previously had come on grass, advancing to the semifinals at a tour event in Birmingham, England in 2010 and 2013 -- both times as a qualifier.
But she was in good form ahead of the meeting with Kvitova, upsetting former Wimbledon semifinalist Tsvetana Pironkova in the first round and German Mona Barthel in the second.
Christina McHale almost joined her compatriot Riske in the fourth round, serving for the match against former world No. 1 Ana Ivanovic.
But Ivanovic broke back and prevailed 4-6 7-5 6-4. Second-seed Victoria Azarenka dropped the first set to France's Alize Cornet in a tiebreak before going through 6-7 6-3 6-2.
Simona Halep, whose four titles in 2013 place her second behind only Serena Williams on the WTA tour, produced the most emphatic score in the women's draw Saturday when she thumped former top-10 player Maria Kirilenko 6-1 6-0 in under an hour.
Kirilenko wasn't only disappointed with her performance -- she didn't like having to provide a sample to drug testers post match.
"I just can (laugh) about my game today!" Kirilenko, engaged to National Hockey League superstar Alex Ovechkin, began on Twitter. "Going to the doping control, maybe I have something after a 0-6! Haha sick of it!!! 1000 times doping doping."
Nadal lost on hard courts to the big-serving Dodig in Canada two years ago but wasn't broken in his 6-4 6-3 6-3 win Saturday.
In remaining unbeaten on hard courts in 2013, he moved closer to a potential quarterfinal showdown with Roger Federer.
Nada's fellow Spaniard, David Ferrer, was slumping before the U.S. Open but the tenacious fourth seed progressed to the fourth round after a four-set win over Mikhail Kukushkin of Kazakhstan.