Williams was making her first appearance at the tournament since winning the title in 2015. She opened with a straight-sets victory against Daria Gavrilova, a match that took just 65 minutes.
Williams also was knocked out in her last tournament at San Jose two weeks ago after reaching the Wimbledon final. Cincinnati was her fifth tournament since she had a baby last September. She has dealt with blood clots and recently said she has been struggling with postpartum emotions.
"You know, this is a long comeback,'' she said. "I just began. I just started -- definitely at the very, very beginning. I'm getting there, and I'm going to just continue to work hard and, hopefully, I'll start winning more matches."
The Associated Press contributed to this report.