Ochoa's bogey-free round moved her to 9-under 135 through 36 holes, one shot in front of Paula Creamer, Angela Park and Angela Stanford.
'It was easy today,' Ochoa said. 'I felt like it was important to be if not in the lead, within one or two shots.
'Now, I'm where I like to be and I can't wait for tomorrow.'
Knocking her drives straight down the fairways and steady with her irons and her putter, Ochoa birdied all four of the par 5s at Big Horn Country club, and made another birdie putt on the par-4 14th.
'I kind of had a lot of confidence in my driver,' she said, noting that she had overcome a tendency to hit the ball to the right that had affected her first round.
Stanford moved into contention with the lowest round of the day, a 66. Creamer and Park, who were tied for the lead after the first day, had second-round 69s.
For Michelle Wie, it was another bad day in a mostly bad year on the course, her round including shots straying into brush and water on the way to her second consecutive 79. She remained in 20th and last place in the elite field.
'I obviously had a tough time today,' Wie said for the second day in a row. 'I made a couple of putts, but there is tomorrow, so I'm going to play better tomorrow.
'I just have to work on my tee shots, but other than that, I think that my irons have been stroking well and are pretty solid. I just have to keep the ball in the fairway and go from there.'
Her shot into a bush on the par-5 seventh and a drop led to a double-bogey 7 there, and a shot into the water at No. 14 cost her another double bogey. Her first 7 didn't look quite so bad, however, compared with the quintuple-bogey 10 playing partner Bettina Hauert of Germany had to write on her card.
Hauert finished with an 81, but held onto 19th place, one shot in front of Wie.
Wie, the Stanford freshman who turned 18 on Thursday, finished 17th in the tournament last year. She made her pro debut in the event in 2005 but was disqualified after the final round for signing an incorrect scorecard for the third round. If she hadn't been disqualified, she would have finished fourth.
Ochoa, the 2006 player of the year and far ahead in the standings this year, came from three shots behind on the final day of the tournament last year to beat Annika Sorenstam. The 25-year-old Mexican star already has won six times this year and earned a record $3,068,421.
Creamer, 21, is threatening for the third consecutive year at Big Horn. She finished second behind Sorenstam in 2005 and was fifth last year.
'I didn't feel like I hit the ball as well as I have,' Creamer said after her second round. 'I hit 11 greens, which is low for me. I missed a lot of opportunities, but I made a lot of up and downs.'
She is third on the money list this year with $1,088,871 in earnings.
The 19-year-old Park, who already has wrapped up this year's rookie of the year award, had six-top 10 finishes in 23 tournaments this season and her $882,476 ranks ninth on the money list.
'I kept it pretty steady out there, nothing exciting,' said Park, still looking for her first tour title. 'I'm glad I kept it close.'