Thompson followed up her 63 on Thursday, which was the low round of her career, with a 3-under 69 at the Senator Course on the Robert Trent Jones Golf Trail.
Her 12-under 132 total gave her a one-shot lead over Mi Jung Hur and Mindy Kim, both of whom had a 65 Friday. Dori Carter, Hee Young Park and Lizette Salas shared fourth place at 134.
Thompson was 16 years old when she won this tournament a year ago, making her the youngest player in history to win an LPGA Tour event. That record was broken last month when 15-year-old Lydia Ko won the Women's Canadian Open.
It took a score of 143 to make the cut and Michelle Wie missed it by one.