Past Grand Slam champions Petra Kvitova and Svetlana Kuznetsova were ousted from the US Open in early upsets on Saturday.
Czech seventh seed Kvitova, the 2011 Wimbledon champion who was reportedly hospitalized on Friday, made 27 unforced errors and seven double faults to lose in only 65 minutes, falling to 81st-ranked US wildcard Alison Riske 6-3, 6-0.
"It's so awesome," said Riske, who lost to Kvitova last week in New Haven in their only prior meeting. "That (result) really helped me to just focus and play my game."
It's also Riske's first trip to the last 16 at a Grand Slam, where she will face either 48th-ranked Slovak Daniela Hantuchova or 128th-ranked Israeli qualifier Julia Glushko, and ensures a first-ever jump into the world top 60.
Russian 27th seed Kuznetsova, the 2004 US Open and 2009 French Open champion who missed last year's US Open with a right knee injury, made 35 unforced errors in losing 7-5, 6-1 to Italy's 83rd-ranked Flavia Pennetta, who had lost their five prior career matchups.
Pennetta, who also ousted Italian fourth seed Sara Errani, will next face Romania's Simona Halep.
Halep, who won her fourth title in the past three months last week at New Haven, breezed into the fourth round at a Grand Slam for the first time by ripping Russian 14th seed Maria Kirilenko 6-1, 6-0 in 51 minutes.
"I'm really happy that I played so good," Halep said. "It was incredible. I played my best match ever."
Kirilenko, the fiancee of Russian ice hockey star Alexander Ovechkin trying to match her best run in 11 US Open visits, was no match for 21st seed Halep, the only WTA player this year to win on grass, clay and hard court.
"I just believed in myself," Halep said. "I'm more confident and more aggressive on court. I want to take the pleasure from every moment."
Halep had missed events at Washington and Toronto with a lower back injury but returned at Cincinnati and downed France's Marion Bartoli in the Wimbledon champion's last career match.