Salas, whose maiden LPGA Tour victory came at last year's Kingsmill Championship, posted a 16-under total of 197 to end the day four ahead of compatriots Lexi Thompson (68) and Kris Tamulis (67).
Germany's Caroline Masson birdied the last three holes for a 65 to finish at 10 under, level with Americans Brittany Lincicome (65), Alison Lee (70), Gerina Piller (69) and Katie Burnett (66), and South Korea's Ryu So-yeon (65).
"I made a couple of little changes after ANA, after missing the cut, and just gradually things have been coming together," Salas told Golf Channel, referring to the year's opening major, the ANA Inspiration in April.
"Hopefully I'll hold up that trophy tomorrow."
Salas tied for 14th in her previous LPGA event, the U.S. Women's Open. "Just coming off a good finish at the Open really gives me that boost of confidence," she said.
Joint leader overnight with Thompson and Lee, Salas made a rousing start with four birdies in her opening nine holes giving her an outward nine of four-under 32 and a two-shot advantage.
Though Thompson briefly cut the lead to one with birdies at 10 and 11, Salas responded with a hat-trick of birdies from the par-three 14th, where she hit her tee shot to within two feet, to storm four ahead and never relinquished her grip.
The long-hitting Thompson, who won her first major title at last year's Kraft Nabisco Championship, was let down by erratic driving.
"I hit it in the rough quite a bit today which didn't allow me to have the birdie opportunities I needed out there," said the 20-year-old American, who is ranked 13th and has five LPGA wins to her credit.
South Korean world number one Park In-bee, who lost a playoff for last year's Meijer LPGA Classic to compatriot Mirim Lee, carded a 66 and stands seven strokes off the pace.
(Reporting by Mark Lamport-Stokes in Los Angeles; Editing by Larry Fine)
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