Fourth seed Sara Errani was ousted from the US Open by fellow Italian Flavia Pennetta on Thursday while Rafael Nadal, Roger Federer and Serena Williams awaited their second-round matches.
Pennetta, ranked 83rd in the world, needed only 71 minutes to take a 6-3, 6-1 victory over her friend Errani, last year's French Open runner-up and a 2012 US Open semi-finalist.
"It was a really tough match," said Pennetta, a former world number 10.
"We know each other really well. It's not easy to play against your friend so well but you have to get on the court and play your best."
Pennetta improved to 4-2 against Errani in their first meeting off clay, smacking seven aces and 33 winners to no aces and only 12 winners for Errani, who was broken in her first three service games of the match, again to end the first set and twice more in the second set.
Facing a friend kept Pennetta from using her more vocally flamboyant stylings on the court.
"When you play against one of your best friends it's not easy to say, 'Come on,' or 'Forza,' really loud. You keep it inside. I played really well today."
Pennetta will next face the winner between China's 37th-ranked Peng Shuai and Russian 29th seed Svetlana Kuznetsova, the 2004 US Open winner.
In another upset, Japan's Kurumi Nara advanced to the third round by defeating Romanian 19th seed Sorana Cirstea 7-5, 6-1.
Nara, a qualifier, next faces Serbian ninth seed Jelena Jankovic, who downed Russian Alisa Kleybanova 6-3, 6-2.
Spanish second seed Nadal, unbeaten on the hardcourts this year to become one of the favorites to claim the crown, will make his bid for a place in the third round in a night match against Brazilian qualifier Rogerio Dutra Silva.
Swiss 17-time Grand Slam champion Federer, at his lowest seed in Flushing Meadows since 2002 at seventh, will meet Argentina's 48th-ranked Carlos Berlocq as he tries to reach the third round, something he could not do at Wimbledon.
Federer lost for the first time in 50 tries in a Grand Slam second-round match last month at Wimbledon, falling to 116th-rated Sergiy Stakhovsky in his earliest Slam exit since the 2003 French Open.
World number one Williams, the defending champion, was to face 77th-ranked Galina Voskoboeva in one of eight women's matches postponed by rain Wednesday.
Kazakhstan's Yaroslava Shvedova put herself into the path of the winner with a 6-2, 6-3 triumph over Austrian Patricia Mayr-Achleitner.