Williams, who was stretched to three sets and saved four match points in her opening match against Samantha Stosur of Australia, beat Sara Errani 6-1, 6-2 in 50 minutes Tuesday.
Her win at Ken Rosewall Arena, the center court at the Olympic Park Tennis Centre, came moments after Safina finished off a 6-3, 6-0 win over Vera Dushevina in just over an hour on Court 1.
Three other seeded players in the women's draw at the joint ATP-WTA tournament also advanced Tuesday.
No. 3 Elena Dementieva beat Jarmila Gajdosova 6-2, 6-4, No. 6 Agnieszka Radwanska defeated Daniela Hantuchova 6-3, 7-5 and No. 8 Caroline Wozniacki beat Melanie South 6-2, 6-0.
In another match, Ai Sugiyama beat Anabel Medina Garrigues 2-6, 6-1, 6-2.
In early first-round men's play, Paul-Henri Mathieu beat Andreas Seppi 6-2, 2-6, 6-3.
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