Safarova came away a 4-6, 6-4, 7-6 (7-3) win over the second-seeded Wozniacki, who was playing her first match since dropping out of the world No. 1 ranking.
Each player saved eight of the 10 break points they faced and were 3-of-4 in saves in the third set. But Safarova had the more solid service game, winning 71 percent of the points on serve, including 69 percent in the third set.
Top-seeded Victoria Azarenka, who replaced Wozniacki at the top of the rankings, was very sharp in her match Wednesday. She had six breaks in a 6-1, 6-0 win over Mona Barthel that took 60 minutes. Azarenka took 70 percent of the points off Barthel's serve.
Seeded players went 5-7 in the second round even with No. 3-seeded Samantha Stosur getting a 6-4, 7-6 (7-5) win over Sorana Cirstea in the 16th match of the day.
Fourth-seeded Agnieszka Radwanska stopped Anne Keothavong 6-1, 6-2 while No. 5-seeded Marion Bartoli routed Anabel Medina Garrigues 6-2, 6-0 and 14th-seeded Svetlana Kuznetsova swept by Maria Kirilenko 6-4, 6-4.
But Monica Niculescu advanced when No. 6-seeded Vera Zvonareva, down 6-5, 3-2, retired; Yanina Wickmayer eliminated seventh-seeded Francesca Schiavone 7-6 (7-4), 6-4; and Shahar Peer beat eighth-seeded Jelena Jankovic 7-6 (7-3), 6-2.
Also Christina McHale stopped 12th-seeded Peng Shuai, Petra Cetkovska beat No. 14 Ana Ivanovic 6-4, 6-4, and qualifier Varvara Lepchenko edged 16th-seeded Julia Georges.
Other seeded players advancing to the third round Wednesday were Simona Halep, Ksenia Pervak, Kateryna Bondarenko and Tsvetana Pironkova.