Li Na, Sloane Stephens, Agnieszka Radwanska, Jamie Hampton and Laura Robson were among the big-name winners on Day 3 while Barty and Venus Williams were two notable losers to be bundled out in the second round of the 2013 US Open.
China's world No. 5 Li Na is comfortably through to the third round after beating Swedish veteran Sofia Arvidsson 6-2, 6-2.
The 31-year-old will next face rising British star Laura Robson who won through to the third round with a 6-4, 7-6 (5) victory also on Wednesday over France's Caroline Garcia.
American 15th-seed Stephens was playing the last match of the night on Arthur Ashe Stadium and didn’t get on the court until after midnight, but the 20-year-old cruised through after losing the first game to beat Poland's Urszula Radwanska 6-1, 6-1.
Stephens will now face another emerging American Hampton in what should be a fascinating third round battle.
The 23rd-seed Hampton won a hard fought straight-set clash with another exciting French talent, Kristina Mladenovic, ending up winning 7-5, 6-4.
Urszula's older sister Agnieszka Radwanska dominated Spain's Maria-Teresa Torro-Flor in the first set and even though she had a tougher time in the second set, the third-seed Pole won 6-0, 7-5.
The third-seed will now play Russian No. 32 seed Anastasia Pavlyuchenkova who advanced to the third round by downing 19-year-old Australian teenager Barty 6-4, 6-0 on Wednesday night.
Barty scored a strong win in the opening round beating Spain's Estrella Cabeza Candela in the first round to win just her second ever Grand Slam singles match.
The biggest casualty of the day was without question Venus Williams though.
The 33-year-old won the US Open twice in back-to-back years in 2000 and 2001, but the seven-time Grand Slam champion has struggled just to get on the court regularly over the past 18 months and now there is the potential she has played her last US Open.
Williams did fight back after losing the first set against China's Jie Zheng in a match that was interrupted by the New York rain, but in the end it was Zheng who prevailed in third set tie-break to end up winning 6-3, 2-6, 7-6 (5).
Zheng will now play Spanish No. 18 seed Carla Suarez Navarro in the third round after she beat American Coco Vandeweghe 6-3, 6-4.
Day 4 women's action will also feature a host of intriguing match-ups.
The battle of Italian veterans Flavia Pennetta and Sara Errani is first up on Arthur Ashe Stadium followed by world No. 1 Serena Williams taking on Kazakhstan's Galina Voskoboeva before at night, former world No. 1 Caroline Wozniacki faces South African Chanelle Scheepers.
German Angelique Kerber is first up on Louis Armstrong Stadium against Canadian Eugenie Bouchard before world No. 2 Victoria Azarenka takes on another Canadian Aleksandra Wozniak.
Another former world No. 1 Ana Ivanovic takes on Romania's Alexandra Dulgheru with other matches of note including Petra Kvitova playing Bojana Jovanovski, Elena Vesnina taking on Karin Knapp, Ekaterina Makarova facing Bethanie Mattek-Sands and No. 10 seed Roberta Vinci is also up against Czech left-hander Lucie Safarova.