Wie held it together with two key par putts and finished with back-to-back birdies for a 2-under 68. Thompson powered her way out of the sand and weeds and ran off three straight birdies to match Wie for the lowest score Friday.
They were the only players still under par going into the weekend, perhaps setting up a rematch from the first major of the year. Thompson soundly beat Wie in the final round at the Kraft Nabisco Championship.
"Definitely too early," Thompson said with a laugh. "Thirty-six holes in a major, that's a lot of golf to be played, especially at a U.S. Women's Open."
For now, Wie had control with a three-shot lead.
The 24-year-old from Hawaii twice thought her shots were going off the turtleback greens, and twice she relied on her table-top putting stance to make long par saves. She finished with a 6-iron that set up a 12-foot birdie putt, and a 15-foot birdie on the par-5 ninth to reach 4-under 136.
"End of the day yesterday, I was thinking if I just did this again, that would be nice," Wie said. "Finishing with two birdies is always great. It's a grind out there. It's not easy. Really grateful for the par putts that I made and some of the birdie putts that I made. I can't complain. I'll take it."
Just when it looked as if this had the trappings of another runaway -- Martin Kaymer led by at least four shots over the final 48 holes to win the U.S. Open -- along came Thompson with a shot reminiscent of what Kaymer did last week.
From the sand and bushes left of the fairway on the par-5 fifth hole, Thompson blasted a 5-iron from 195 yards just off the green, setting up two putts for birdie from about 60 feet. Kaymer was in roughly the same spot in the third round when he hit 7-iron from 202 yards to 5 feet, that pin position more toward the front.
That was her third straight birdie, and she closed with four pars to reach 139.
Pinehurst No. 2 wasn't in much of a giving mood on another warm day in the North Carolina sandhills, with a brief shower in the middle of the afternoon that didn't do much to soften a dry, crusty golf course.
Stacy Lewis, the No. 1 player in women's golf who opened with a bogey-free 67, picked up a bogey on her first hole in a wild round of six bogeys, three birdies and a tough 73. A two-time major champion, she saw the big picture.
"I hung around, and that's what you've got to do at this tournament," said Lewis, at even-par with Amy Yang (69) and Minjee Lee, the 18-year-old amateur from Australia who played bogey-free on the back nine to salvage a 71.
Lucy Li, the precocious 11-year-old and youngest qualifier in the history of the U.S. Women's Open, isn't leaving town until Monday. She just won't be playing any more golf. The sixth-grader from the Bay Area started with a double-bogey for the second straight day and shot another 78 to miss the cut.
The cut was 9-over 149.
A couple of the LPGA Tour's most recognizable names didn't make it to the weekend.
Cristie Kerr, who won the Women's Open the last time it was held in the North Carolina sandhills in 2007, was at 10-over.
Cheyenne Woods -- Tiger's niece -- had six bogeys during her 75 and was at 13-over. And Morgan Pressel was at 12-over following her 75.
No one was conceding anything to Wie or Thompson. What last week showed was a Pinehurst No. 2 that played about the same all four days, instead of some U.S. Opens where scores are thrown in reverse on the weekend. There's still plenty of time for players to chip away at par, and equal opportunity to lose even more ground.
"When you think seven shots, you think that's a lot," Karrie Webb said after battling for a 73, leaving her seven shots behind. "But really at the U.S. Open, I don't think that's too far out."
Na Yeon Choi had a 70 and was at 1-over 141, followed by a Paula Creamer (72) at 2-over 142. The group at 143 included Webb and So Yeon Ryu, who saved her hopes with three straight birdies on the front nine, and narrowly missing a fourth. All of them are former Women's Open champions.
This is a different Wie they are chasing.
She is in contention on the weekend in her second straight major. The last time that happened was when she was 16 and had a chance in three of them. Wie already has won this year in Hawaii, and she has eight top 10s and is No. 2 on the LPGA money list.
Attribute that to a putting stroke that she owns, no matter how peculiar it looks with her back bent severely, almost parallel to the ground. And she has learned to play the shot -- she has a full allotment -- instead of worrying about her score or her position on the leaderboard.
"I think you look at the way Michelle has played the last six months and you look at her differently," Lewis said. "I think she's become one of the best ball-strikers on tour. She hits it really consistent. She knows where the ball's going. And she's figuring out how to win. That's the big thing."
Information from the Associated Press was used in this report.
Strong Round 2 For Wie
Michael Collins catches up with Michelle Wie after Round 2 of the U.S. Women's Open.
Li Misses Cut As Wie Grabs Lead
Lucy Li's historic week at the U.S. Open came to an end as she finished the second round with another 78, while Michelle Wie closed with two birdies for a second straight 2-under 68.
Prodigies Making Impact At U.S. Women's Open
Mechelle Voepel and Michael Collins discuss Lucy Li's showing at the U.S. Women's Open and the pairing of Michelle Wie and Lexi Thompson in the third round.
Thompson Trails Wie Heading Into Weekend
Lexi Thompson talks about her second round and making the final group for the third round of the U.S. Women's Open.