The 40-year-old Australian, a seven-times major winner, started at the 10th and after a steady tour of Lancaster Country Club’s difficult back nine posted birdies at the second, fourth, sixth and eighth holes on the way home.
“I feel like I’ve had some good golf in me,” said Webb, who has three top-10s in recent months including a share of seventh place last month at the Women’s PGA Championship.
Tied at 66 was little-known American Marina Alex, who also took advantage of rain-softened conditions on the long, hilly layout with three birdies on the front nine.
Late in the afternoon wave of players, a tornado watch in the area gave way to a halt of play as the skies darkened, thunder boomed and heavy rain fell on Lancaster Country Club in the heart of Pennsylvania’s Amish area.
After a two-hour wait, play was called off for the day with more than 50 players yet to finish the first round.
One stroke back was South Korean Amy Yang after a 67, with 2012 winner Choi Na-yeon of South Korea also at three-under, through 15 holes, along with American Jane Park, through 13.
“I drove the ball really well today,” said Yang. “Staying in the fairway is key on this course.”
They were followed by six players in the clubhouse at 68.
Morgan Pressel, who had reached four-under by her 14th hole of the day before slipping back, was among those at 68 along with fellow Americans Austin Ernst, Sydnee Michaels and Liz Nagel, and South Koreans Chun In-gee and Lee Mi-hyang.
Amateurs Regina Plasencia of Mexico and American Megan Khang also reached four-under before falling back.
Khang, 17, birdied four of five holes from the third before following with five bogeys to card a 71.
Plasencia, 21, also had four front-nine birdies before a double-bogey at the par-three eighth hole began a slide that took her to even-par through 12 holes.
World number one Park In-bee of South Korea stood two-under through 14 holes when the weather delay struck, along with 16-year-old Chinese amateur He Mu-ni, who had completed 11 holes.
Another shot back was a large group at one-under 69 that included world number three Stacy Lewis, who was one shot better than second-ranked Lydia Ko of New Zealand.
Webb, whose last major triumph came nine years ago at the Kraft Nabisco, played a remarkably solid round.
The winner of 41 career LPGA titles hit every fairway and 17 of 18 greens in her impressive round.
Webb, who won the first of her back-to-back U.S. Open crowns 15 years ago, said she is still driven by competition.
“Playing rounds like this is what motivates me. I’ve worked really hard over the last year, because I changed coaches.
“The swing is starting to be a little more automatic,” said Webb. “I don’t have to think about what body part moves when.”
Webb praised the setup of the course. “I used every club in my bag except the six-iron,” the Australian said. “When they set up a course like that to use every club, it’s a good setup.”
Some notable players struggled.
Cristie Kerr, the 2007 winner, was six-over after 15 holes, while two-times major winner Suzann Pettersen of Norway shot 79.
(Editing by Mark Lamport-Stokes)