Defending champion Dinara Safina, recovered from a back injury, lost her opener against Alexandra Dulgheru of Romania 6-4, 6-7 (5), 6-1.
Top-ranked Serena defeated Timea Bacsinszky 7-6 (2), 6-1 in her first match since winning the Australian Open more than three months ago. No. 4-ranked Venus, taking to the center court at the Foro Italico just before her sister, handled veteran Patty Schnyder 6-2, 6-2.
Serena was down 4-1 and saved three set points at 5-4 before going to a tiebreaker against Bacsinszky. After dominating the breaker, Serena ran off the next four games to secure the match.
Serena said she “felt good” in her first match since January and that, after falling behind, she needed to pick up her game and get her rhythm back.
“It's a start,” said the 28-year-old American.
Venus had an easier time against Schnyder, a lefty who had defeated Serena in Rome last year. Venus was always in control of the match, breaking the Swiss player six times.
Venus had been sidelined since losing the Key Biscayne final a month ago.
“I think it was a pretty good performance. I felt good on court,” Venus said. “She probably likes clay with her type of game and I was able to execute pretty well out there on the court.” The sisters, former Rome champions, are preparing for the French Open, which begins on May 23.
The third-seeded Safina struggled for 2 hours, 40 minutes with her opponent and her own erratic game.
She recovered from 4-0 behind to level at 4-4 but went on to lose the next two games and the set to Dulgheru. After taking the second set in a tiebreaker, Safina had a disastrous third set, firing mistakes from both sides of the clay court.
Finding herself down 5-0, she twice smashed her racket in frustration. She sent a forehand wide to give the match to Dulgheru, who hadn't beaten anyone in the top 30 until now.
“In a second I was 5-0 after winning the second set,” Safina said. “I think the only good thing about this match was that my back didn't create any problems.” A recent No. 1, Safina retired from the Australian Open in January with a lower back injury, and in her first tournament back - last week's Porsche Grand Prix - she lost in the quarterfinals.
In other results, two-time former champion Jelena Jankovic defeated Bethanie Mattek-Sands of the United States 6-3, 3-6, 6-1, eighth-seeded Agnieszka Radwanska beat Roberta Vinci of Italy 6-1, 6-0, and Shahar Peer of Israel came from behind to beat Polona Hercog of Slovenia 2-6, 7-5, 6-3.
