Ochoa shot a 7-under 64 at the Kingsmill River Course for a one-shot advantage over Lindsey Wright.
After morning rains, the weather quickly improved and low scores were plentiful.
Wright did not suffer a bogey to finish alone in second and those in third place at 66 included Sarah Lee, Hee-Won Han and Minea Blomqvist.
"It was a good start," said Ochoa. "In the morning it was raining and I thought it was going to be a long day. I was planning for it to be a delay. But it ended up being fine."
Ochoa won the most recent stop on the LPGA circuit in her native Mexico.
"I don't want to put pressure on myself," she said. "It's just one more week, one more great tournament."
Ochoa has never won at Kingsmill. She finished 12 shots behind champion Annika Sorenstam last year.
Copyright 2009 by United Press International.