Serena Williams improved to 15-0 on clay courts this year, rallying for a 4-6, 6-2, 6-3 win over Russian Nadia Petrova.
The American star and former world No. 1 advances to take on Spaniard Anabel Medina Garrigues.
Venus Williams, playing in Rome as a wild card, topped Ekaterina Makarova 7-6 (9-7), 6-1 at the Foro Italico, advancing to face Australian Samantha Stosur, who got past Italian favorite Sara Errani 6-3, 7-5.
Wednesday's Day 3 produced a pair of upsets.
World No. 3 Agnieszka Radwanska of Poland was upended by Czech Petra Cetkovska 6-4, 4-6, 6-1, while former No. 1 Caroline Wozniacki retired with an upper respiratory illness during her 6-4, 4-0 loss to Medina Garrigues.