The 47-year-old Inkster is vying to become the oldest player to win an LPGA Tour event. She finished at 6-under 210 on a tough day for scoring because of swirling winds, tricky flag positions and difficult greens. Only seven players broke par.
Jang Jeong of South Korea is second after a 72, followed another shot back by Sophie Gustafson of Sweden (72), Shin Ji-yai of South Korea (70) and Diana D'Alessio of the United States (76).
The 17-year-old Wie had the worst round of the day, shooting 12-over par to languish in 69th place. She had four double bogeys, five bogeys and one birdie in her round. 'It was frustrating,' Wie said. 'My body would not do what my mind was telling it to do. I felt a little out of whack.'
Wie, who is recovering from wrist injuries, shot a 71 on Friday. She had gone 24 consecutive rounds without breaking par. On Saturday, Wie hit only three of 14 fairways, five of 18 greens and had 32 putts.
'That is what happens when you recover, you have some bad days and you have some good days,' she said. 'But I'm still going to take some positives out if and work on it tomorrow. It was a very unfortunate round.'
Two-time winner Annika Sorenstam (74), Natalie Gulbis (73) and Chung Il-mi (70) were four strokes behind the leader.
Inkster, who won in 2003, needed only 26 putts, and credited her confidence on the greens to a recent putting lesson.
She laid up at the 18th hole with water in front of the green and hit a sand wedge to 3 feet for a birdie.
'If it was Sunday and I was behind by one, I'd go for it, but it was too risky a shot for Saturday,' Inkster said.
If she wins Sunday, she'll top JoAnne Carner, who won the Safeco Classic at 46 in 1985. The Evian Masters became an official LPGA Tour event in 2000.
Defending champion Karrie Webb (73) and Laura Davies (74) were among four players five strokes back. Lorena Ochoa (75) is seven shots behind Inkster.
The 84th-ranked D'Alessio shared the second-round lead by three strokes with Jin-joo Hong, who struggled to an 80 Saturday. D'Alessio was leading the tournament at 8 under at the turn before she had a quadruple bogey at the 12th.
'What a nightmare,' D'Alessio said. 'I was cruising along then it was: 'Welcome to reality.' The 12th was a comedy of errors ending with a four-putt.
'Overall, I'm not too unhappy with my position in the tournament. I'll go to sleep tonight, forget about it and hope for better things tomorrow.'