Park, the 2007 LPGA Rookie of the Year, shot a bogey-free round on the 6,397-yard, par-72 course.
Kelli Kuehne was in a group of six tied for second at 67 with Hee Young Park, Song-Hee Kim, Sophie Gustafson, Helen Alfredsson and Karen Stupples. Stephanie Louden, Liz Janangelo, Becky Morgan, Katie Futcher and Hee-Won Han were two strokes behind.
Angela Park started quickly, carding birdies on four of her first seven holes on the way to a 4-under 32 on the front nine. She moved to 6 under at 13, and made pars the rest of the way to finish her round.
Kuehnes round was one of the most dramatic Friday. She was 3 over after five holes, having made a double bogey at No. 1. Kuehne then recorded birdies on five of her next seven holes and was 8 under during her final 13.
Kim was 1 over through seven holes, before making birdies on six of her final 11. Defending Safeway champion Lorena Ochoa was three shots back at 69.
Among those joining Ochoa were Paula Creamer, Laura Diaz and Leta Lindley. Ochoa, the seasons earnings leader with $2,337,206, birdied the final three holes to put herself into contention.
Ochoa capped her round by sinking a 50-foot birdie putt at 18. U.S. Womens Open champion Inbee Park and Karrie Webb were among those to shoot 70. Katherine Hull, who won the Canadian Womens Open on Sunday, shot a 71.
Annika Sorenstam, a two-time Safeway Classic winner, birdied her final hole to shoot 72. Pat Hurst, who won the 2006 Safeway, finished with a 75.
There was speculation heading into the tournament about how difficult Columbia Edgewater would play because of recent heavy rain. With the course drying out from Fridays 80-degree temperatures, 55 players in the field of 150 broke par.
The $1.7 million Safeway Classic, the longest running non-major on the LPGA Tour, attracted a field that includes 28 of the seasons top 30 money earners.