China's Yuan Meng ousted Sania Mirza in straight sets to cap a difficult day for seeds at the East West Bank Classic in Los Angeles on Wednesday.
The 16th seeded Indian served six double faults as she went down 4-6, 3-6 to Meng, ranked 122 in the world in the second round.
Meng will take on Great Britain's lucky loser Melanie South, who beat Czech Petra Kvitova 6-4, 6-2.
Swiss Patty Schnyder and Nicole Vaidisova of the Czech Republic were the other seeded players to make an exit in the second round.
Yuan Meng (China) beat 16-Sania Mirza (India) 6-4, 6-3
10-Flavia Pennetta (Italy) beat Tamira Paszek (Austria) 2-6, 6-1, 6-4
14-Sybille Bammer (Austria) beat Stephanie Dubois (Canada) 6-3, 7-5
Bethanie Mattek (US) beat 11-Nicole Vaidisova (Czech Republic) 6-4, 6-0
8-Victoria Azarenka (Belarus) beat Chan Yung-Jan (Taiwan) 6-1, 6-3
9-Nadia Petrova (Russia) beat Akgul Amanmuradova (Uzbekistan) 6-1, 3-6, 6-1
4-Dinara Safina (Russia) beat Peng Shuai (China) 6-2, 6-2
Samantha Stosur (Australia) beat Regina Kulikova (Russia) 7-6(4), 7-5
Melinda Czink (Hungary) beat Olga Savchuk (Ukraine) 6-4, 2-6, 6-4
Ai Sugiyama (Japan) beat 7-Patty Schnyder (Switzerland) 6-4, 7-5