Pettersen, two strokes off the pace overnight at the year's third Major, fired a sparkling four-under-par 68 on a slightly cooler day at Blackwolf Run to grab a one-shot lead with a five-under total of 139.
Wie was in hot pursuit, a best-of-the-week 66 lifting her into a share of second place with fellow American Cristie Kerr, who carded a 71.
Germany's Sandra Gal (70), South Korea's Park In-bee (70) and American Vicky Hurst (70) were a further stroke back at three-under 141.
Pettersen, who won her first Major title at the 2007 LPGA Championship, was delighted with her position going into weekend after launching her second-day charge with four birdies in her first seven holes.
"I got off to a very good start, hit a lot of the shots I tried to hit, and just tried to execute my game plan," the 31-year-old Norwegian said after mixing five birdies with a bogey at the par-four fourth.
"There are definitely low scores and birdies out there, so I'm very happy where I'm at. I can put my legs up now and rest a little bit."
Pettersen surged up the leaderboard with birdies at the 10th, 12th, 14th and 16th after starting out on the back nine.
Though she bogeyed the fourth, she recovered with a birdie at the eighth to retain the outright lead.
"The course is very playable," she said. "You hit the fairways, you give yourself a lot of chances out here. The greens are rolling perfect.
"You don't try to attack every pin. You try to give yourself some makeable putts on the more difficult holes, and the few holes where you feel you can be aggressive you have to try to step on it."
Wie, who has yet to live up to the lofty expectations heaped upon her when she turned professional in 2005 at the age of 15, captured the spotlight at Blackwolf Run with a sizzling seven-birdie display.
"It went well today," beamed the 22-year-old Hawaiian. "It was just fun. I just went out there and kind of tried to be patient. When putts started dropping in, it makes for a low round.
"But it's only halfway done. I got a long way in front of me. I'm really glad I shot the score I did today and that I'm back in contention. I'm really looking forward to this weekend."
Wie, who has triumphed twice on the LPGA Tour but has yet to win a Major title despite several close calls, felt the course was a little easier to play on Friday.
"For starters it wasn't quite as hot, which is nice, and the pins are a little bit more in the centre today than yesterday," she said. "But overall it's still a US Open golf course. I played out of my butt today to shoot six-under."
Taiwan's world number one Yani Tseng, who opened with a 74, carded a 72 to end the second round seven strokes behind the pacesetting Pettersen.
Long-hitting Brittany Lincicome, joint leader overnight with Kerr and fellow American Lizette Salas, battled to an 80 to finish at five-over 149, making the cut right on the number.
"I did nothing right today," the 26-year-old said. "I couldn't drive the ball. I couldn't putt.
"You go out and feel like you did so good yesterday and I have no idea what happened today. You get it in the wrong place here and there, and it's tough."