Pettersen, ranked sixth in the world, overcame a strong breeze at the Turnberry links to shoot a three-under-par 69 for a seven-under tally of 137.
"They were very tough conditions, the ball is going nowhere," the 34-year-old told reporters. "Par is a very good score today.
"I felt I was in 100 percent control of the ball, the flight, the spin, everything you need to do in conditions like this," said Pettersen who is chasing the third major championship of her career.
World number two Lydia Ko of New Zealand carded a 73 to share second place on 139 with South Korean pair Ryu So-yeon (72) and Ko Jin-young (71) and Taiwan's Teresa Lu (71).
"It was really difficult," said 18-year-old Kiwi Ko. "The wind... was definitely a totally different direction to what it was yesterday so the course was kind of like playing a new course."
South Korea's world number one Park In-bee was five strokes off the pace after returning a 73.
Defending champion Mo Martin and fellow Americans Paula Creamer, Juli Inkster and Morgan Pressel missed the cut, as did 51-year-old Briton Laura Davies and Australia's Karrie Webb.
(Writing by Tony Jimenez, editing by Ken Ferris)
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