The 22-year-old is eight under, two clear of compatriots Mirim Lee (74) and Amy Yang (71) at CordeValle.
"Coming to the tournament, I didn't even think about winning because this is the first time for me," Park said.
England's Jodi Ewart Shadoff is the leading European after a 71 saw her into a tie for 10th on three under.
She will be joined over the weekend by Scotland's Catriona Matthew, who posted a 72 to sit one-over.
But the remaining British contenders - Charley Hull, Pamela Pretswell, Melissa Reid and Hannah Burke - all missed the cut.
World number one Lydia Ko is three shots adrift in fourth place after matching Park's 66.
Park, who only made her debut on the LPGA tour last year, tied for sixth in her first major at the ANA Inspiration in April.
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South Korea's Sung Hyun Park posted a six-under-par round of 66 to open a two-shot lead at the halfway point of the US Women's Open in California.