While Williams' brilliant resume includes 61 titles the Cincinnati hard court event is not on that long list and the 32-year-old American has set her sights on a adding it to her collection.
In five previous visits Williams, a 17-times Grand Slam champion, has only reached the semi-finals twice with her best result coming last year when she let the title slip through her fingers losing in a third set tiebreak to Victoria Azarenka.
"I love coming here, it's fun," said Williams, who is a perfect 12-0 on American hard courts this season. "I like it because it's in America, as well, and it's so good to play some tournaments in the United States.
"Being an American, it just feels like you're at home. Even though it's not your home state it's your home country, so it's a great feeling."
Williams looked completely at home on Thursday and in control right from the start as she raced to a 3-0 lead in the opening set then cruised through the second after charging in front 5-0.
"I got an early break on and I just didn't let go," said Williams, who will defend her U.S. Open crown later this month. "That's what I wanted to do, because she can try to come back. Even in the end she tried to make a comeback.
"But I knew I needed to kind of stay focused."
In other action fast rising Ukrainian teenager Elina Svitolina followed up her second round stunner over Wimbledon champion Petra Kvitova with another upset, advancing with 4-6 6-4 6-4 win over 15th seed Carla Suarez Navarro of Spain.
French Open champion Maria Sharapova also advanced with a victory against Anastasia Pavlyuchenkova 6-4 7-6 (2).
Sharapova's win sets up a match against Simona Halep, who she beat in the Roland Garros final after the Romanian beat Lucie Safarova 6-4 7-5 to advance.
Cincinnati Open results
12-Caroline Wozniacki (Denmark) beat 6-Angelique Kerber (Germany) 7-5 6-2
4-Agnieszka Radwanska (Poland) beat Sabine Lisicki (Germany) 6-1 6-1
9-Ana Ivanovic (Serbia) beat Svetlana Kuznetsova (Russia) 6-2 2-6 6-3
5-Maria Sharapova (Russia) beat Anastasia Pavlyuchenkova (Russia) 6-4 7-6(2)
8-Jelena Jankovic (Serbia) beat Sloane Stephens (U.S.) 7-6(4) 6-4
Elina Svitolina (Ukraine) beat 15-Carla Suarez Navarro (Spain) 4-6 6-4 6-4
1-Serena Williams (U.S.) beat 13-Flavia Pennetta (Italy) 6-2 6-2
2-Simona Halep (Romania) beat 16-Lucie Safarova (Czech Republic) 6-4 7-5
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