Serena, Azarenka pull out of Cincy
Former world number one Williams, who returned to competition in June after missing 11 months with injuries and health problems, said her latest setback is related to a prior toe issue but is not as serious.
"It is not nearly as extreme. It's just a bit of an aggravation because I think I've been pounding it a lot and playing a lot," said Williams, who admitted to feeling some discomfort during her win on Tuesday.
"But I don't think this is a good time for me to take a big chance. I just don't think that would be smart."
The 13-times Grand Slam champion, who triumphed in her last two tournaments, was due to face Australian 10th seed Samantha Stosur in the second round, in a rematch of the Toronto Cup final she won Sunday.
After her straight sets victory over Czech Lucie Hradecka Tuesday, Williams said she was wary of becoming tired before the US Open later this month.
The American said the decision to withdraw could benefit her with more time to rest before the year's final grand slam in New York.
"I'm definitely disappointed, but at the same time, I have a lot to look forward to," she said. "If anything, this might be a blessing in disguise. I might get some more rest and prepare for the rest of the year."
Despite the injury, Williams said she may now attend her celebrity friend Kim Kardashian's wedding this weekend to New Jersey Nets basketball player Kris Humphries.
"Now that I have time I probably will," said Williams. "I hadn't thought about it."
Belarussian Azarenka announced she was withdrawing due to a "right hand strain" shortly before her second round match against Israeli Shahar Peer.
Pauline Parmentier of France took Azarenka's place against Peer.