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.
The two are close friends and teammates on Italy's Fed Cup team.
Pennetta was the first Italian woman ranked in the top 10, but has fallen to 83rd. Her slide began when she missed the end of last year, including the US Open, with a right wrist injury.
Errani was the French Open finalist and a semi-finalist at the US Open last year but has made it past the second round in only one of the four majors in 2013.
"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.