Williams has moved back to number six in the world rankings
Serena Williams began her bid for a fourth successive title in 2008 with victory over Francesca Schiavone in round two of the German Open.
The American fifth seed, who had a first-round bye, extended her winning streak to 16 matches with a 6-2 6-3 defeat of Italy's Schiavone.
Top seeds Justine Henin and Ana Ivanovic join the action on Wednesday.
"I'm healthy, I'm focused, tennis is my priority. Everything is just coming together," said Williams.
"Obviously, I would like to keep up the streak. I really want to keep it up on clay. I can slide on clay and be a little bit more lazy - I like that.
"This was a good first match, she's a great player to play against. I served well and that keeps me happy."
Seventh and eighth seeds Elena Dementieva and Marion Bartoli enjoyed comfortable opening wins.
There was disappointment for 12th seed Nicole Vaidisova, playing for the first time since linking up with British coach David Felgate last month.
The 19-year-old Czech lost 4-6 6-1 6-2 to Argentina's Gisela Dulko, who went into the match on the back of her third WTA tournament win in Morocco on Sunday.
Amelie Mauresmo pulled out of the tournament on Monday with rib pain.