JOIN USSerena struggles into quarters
The American had a sticky patch against unseeded Petkovic, after having taken her time to get going against Swiss Timea Bacsinszky on Tuesday in her first match since winning January's Australian Open.
However she has already shown in Rome an ability to raise her game when needed, an attribute she is likely to have to call upon at this month's French Open.
Williams looked comfortable in the first set, reading her opponent's beefy serve well and using Petkovic's power to crack some sizzling return winners.
She was swinging the racket with gusto at the start of the second set, with a gorgeous net volley and an emphatic smash helping her to hold to love in the second game.
Williams then began attacking the ball too early, leading to unforced errors that let the German off the hook when she was under pressure in the following game.
The world number one's rhythm suddenly went astray and she was broken twice on the way to losing the second set, bouncing her racket on the ground in frustration when a netted forehand clinched it for Petkovic.
Williams regained her concentration though to win the decider without dropping a game. On Tuesday, Williams announced her return from injury by overpowering Swiss Timea Bacsinszky 7-6, 6-1.
The American, who suffered a knee injury after beating Justine Henin to lift the Australian title in Melbourne after a three-set battle, looked listless in the early stages of her second-round match and struggled on serve.
Bacsinszky capitalised, mixing things up nicely with her drop shots especially effective against a leg-weary Serena and unleashing eye-catching winners from both sides to break twice and race 4-1 ahead on the red clay surface.
Williams clawed her way back, despite a few erratic moments, saving three set points on her opponent's serve before dominating the tiebreak and the second set to book a meeting with Germany's Andrea Petkovic.
Denmark's world number two Caroline Wozniacki dropped just one game in her 6-1, 6-0 win over Italian wild card Maria Elena Camerin. Serbian Ana Ivanovic, who has slipped to 58th in the rankings after being top two years ago, showed she might be on her way back to form by beating ninth seed Victoria Azarenka 6-4, 6-4 to set up a clash with world number six Elena Dementieva who beat Yaroslava Shvedova of Kazakhstan 6-4, 7-5.
Reuters