Park, who has three wins on the Korean Tour and is playing her first season on the LPGA circuit, birdied seven of her first 16 holes on the way to a sparkling six-under-par 66 at CordeValle Golf Club in San Martin, California.
Though she bogeyed her penultimate hole, the par-four 17th, her eight-under total of 136 put her two strokes clear of fellow Koreans Amy Yang (71) and first-round leader Lee Mirim who fell with a two-over-par 74.
New Zealander Ko, seeking her third major title at the age of 19, followed her opening 73 with a seven-birdie 66 to surge up the leaderboard, finishing the day just three shots off the pace.
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"I didn't start off very well, missing the fairway on one," Ko, who began her round with a bogey and ended it with a four-foot putt for birdie at the last, told reporters.
"But my birdie on three kind of turned the round around and making the string of (four consecutive) birdies definitely helped.
"I'm playing on the Tour that I've always dreamt of playing, and this is the biggest championship in the U.S.” said Ko, who won her first major title at last year's Evian Championship before adding a second at the ANA Inspiration in April.
“There's a lot of golf to be played, so I don't really want to get ahead of myself.”
Ko's two playing competitors in a marquee group, Canadian world number two Brooke Henderson (71) and fourth-ranked American Lexi Thompson (73), each ended the day at three-over to narrowly make the cut.
Lee had vaulted to a three-stroke advantage after a 64 Thursday morning, but on Friday she got the tougher afternoon draw, as the course firmed and the wind picked up, and endured a roller-coaster round that featured four birdies, four bogeys and a double bogey.
Korean Park, who made her LPGA Tour debut at the Founders Cup in March, said she had benefited from a strategy of simply enjoying herself on the course.
"Coming to the tournament, I didn't even think about winning because this is the first time for me," she said of her maiden U.S. Women's Open.
"I'm trying to enjoy this tournament. That's why I am comfortable, don't even think about the winning."
(Reporting by Mark Lamport-Stokes and Jahmal Corner; Editing by Andrew Both/Amlan Chakraborty)
