Top-ranked Lorena Ochoa, 2007 champion Cristie Kerr and qualifier Jean Reynolds opened with 2-under 69s, and Hee Young Park, also of South Korea, was another stroke back after 70.
Birdies were tough to come by for nearly everyone but the 21-year-old Choi, who has won four times in international events.
Choi made Saucon Valley's narrow fairways seem wide and handled its speedy, undulating greens. She relied on accurate approach shots throughout and reached 5-under by her 12th hole, before backing up just a bit. Starting on the back nine, Choi had consecutive bogeys on the 409-yard, par-4 fifth, and 559-yard, par-5 sixth before closing with three pars.
Ochoa started early today on the back nine and offset two bogeys with two birdies on her first nine and then moved below par with consecutive birdies at Nos. 2 and 3.
On the par-4 second hole, she rolled in one of the longest putts of her career a putt that moved right, left, up and down before falling for a 3.
Kerr hit 15 greens and 10 fairways in a round of three birdies and a bogey, using her knowledge and confidence of being a former Women's Open champion on the challenging Old Course. She drained birdie putts of 15, 12 and 8 feet and shrugged off her only bogey.
Reynolds, a two-time winner on the Futures Tour and the leading money winner on the LPGA's developmental tour, had four birdies and two bogeys.
Reynolds opened with a birdie at the first and made a strong par save at the second hole after driving into a fairway bunker. She hit a 7-wood to about 45 yards and got up-and-down.
She used pinpoint accuracy with her approach shots to move into contention, hitting to within a foot at the first, 3 feet at the eighth and 8 feet on the 14th. She also got up-and-down from a greenside bunker at No. 12.
LPGA Championship winner Anna Nordqvist, a 22-year-old rookie from Sweden, is in a six-way tie for sixth at even-par 71 with Candie King, Eun Hee Ji, amateur Alexis Thompson, Kristy McPherson and Young Kim.
Former champion Laura Davies, who received a special exemption that extended her streak of competing in championships to 24, opened with 1-over 72, as did 14 others, including Paula Creamer, Christina Kim, Brittany Lincicome and three amateurs.
Defending champion Inbee Park opened with 4-over 75, and two-time champion Juli Inkster made her 30th straight Open start and shot 7-over 78.