Former world No. 1 women Ana Ivanovic and Victoria Azarenka both needed three sets to overcome their opponents on Saturday at Flushing Meadows to move through to the fourth round.
However, Caroline Wozniacki wasn’t quite as lucky losing in three sets while former major winners Svetlana Kuznetsova and Petra Kvitova both lost in straight set upset defeats.
Serbian 13th-seed Ivanovic took part in an incredible three-set battle with American Christina McHale and eventually prevailed 4-6, 7-5, 6-4 on Arthur Ashe Stadium.
Ivanovic will now next face world No. 2 Azarenka who also had a tough battle against the ever-improving French No. 26 seed Alize Cornet.
However, Azarenka was able to bounce back after losing the first set in a tie-break to take out the match 6-7 (2), 6-3, 6-2 over Cornet and now a fascinating battle between the Belarusian and Serb awaits in the round of 16.
Dane Wozniacki is seeded No. 6 at the US Open but was No. 1 for 67 weeks between 2011 and 2012, and she started her third round clash with Italian Camila Giorgi by winning the first set, but she couldn’t go on with it.
The 137th-ranked Giorgi ended up winning the match 4-6, 6-4, 6-3 to set up a fourth round clash with her fellow Italian Roberta Vinci.
The 10th-seed Vinci had little trouble beating another Italian in the third round, downing Karin Knapp 6-4, 6-3 on Saturday.
Another upset in women's action on Day 6 saw Romanian 21st-seed Simona Halep thrash the 14th-seeded Russian Maria Kirilenko 6-1, 6-0.
That will now see Halep take on Italian veteran Flavia Pennetta in the fourth round after the 31-year-old upset two-time Grand Slam winner Kuznetsova 7-5, 6-1 in the third round on Saturday.
That continued a tremendous run already at this year's US Open for Pennetta as she has now beaten Nicole Gibbs, Sara Errani and Kuznetsova to win through to the fourth round.
Perhaps the biggest casualty of the day, though, was 2011 Wimbledon champion Kvitova.
Clearly hampered by a recurrence that also felled her at Wimbledon, the seventh-seeded Czech was able to win just three games in the first before losing to American Alison Riske, 6-3, 6-0.
Riske will now take on a resurgent Slovak Daniela Hantuchova who beat Israeli Julia Glushko 3-6, 7-5, 7-6 (4) after having to save four match points along the way.
Hantuchova first broke through onto the scene with three straight Grand Slam quarter-final appearances between 2002 and 2003, but despite an Australian Open semi-final appearance in 2008, it has been relatively slim pickings for her since.
This year's US Open fourth round appearance is now the first time she has reached the round of 16 at a major since achieving it also at the 2011 French Open.
Before this year's US Open, the 30-year-old who is now ranked 45th in the world after being as high as 5 in 2003 had lost five straight first round Grand Slam matches but now could get through to her first quarter-final since 2008.
It is now set for a massive Day 7 of women's action at the US Open with the undoubted highlight being the battle between American pair Serena Williams and Sloane Stephens. That match will be third up on Arthur Ashe Stadium.
The night clash on Arthur Ashe pits Jelena Jankovic up against Li Na while on Louis Armstrong Stadium, Carla Suarez Navarro plays Angelique Kerber, and Agnieszka Radwanska plays Ekaterina Makarova.