The third seeded Indian ace was particularly effective with her returns, breaking Lepchenko five times during the one hour and eight minutes Tier III match.
Sania, who lost to Akiko Morigami in the quarter-finals of the tournament in 2005 and Patty Schnyder at the same stage last year, said she had planned to skip the tourney.
"It's funny. When I was deciding my schedule I wanted to skip Cincinnati, but my dad said, 'Oh, but you always play well in Cincinnati'," Sania said.
"The conditions suit me and the court suits my game. I play well. I also like the city because it feels a lot like India here because of the conditions. I've played well here all three years that I've come here, and I hope to win my next match," she added.
The 38-ranked Sania is working her way back into shape after missing two-and-a-half months earlier this season due to knee surgery.
"I hadn't played her in like seven years -- I mean we played Under-13s together -- but I kind of knew what I had to do today.
"I think I'm getting used to the court more after having played a few matches in singles and doubles. I feel like I'm hitting the ball better now. I just want to keep going, keep improving," said the 20-year-old Hyderabadi player.
She now awaits the winner of the second round match between ninth-seeded Jill Craybas of the United States and Olga Govortsova of Belarus..
Photograph: Matthew Stockman/Getty Images