Lewis shared the first-round lead with Brittany Lincicome and moved in front by herself with a 3-under-par 69 over the heat-seared Mission Hills Country Club course.
She scrambled her way to the lead with a two-day total of 9-under 135.
"I was all over the place, but I made some really good up-and-downs and stayed really patient," Lewis said. "I got away with a couple of pars that I probably shouldn't have."
Yani Tseng, the top-ranked player in women's golf, shot a 68 to move into a share of second place with Jane Park and Lincicome at 138.
Lincicome won this tournament three years ago by making an eagle on the final hole.
Amy Yang and Morgan Pressel were tied for fifth at 139. Sophie Gustafson was alone in sixth at 140.
Michelle Wie bounced back from a poor first round to shoot a 67 and was in the tie for eighth place at 141. Sandra Gal, who won her first LPGA Tour event last week at the Kia Classic, was also at 141.