The 17-year-old fired a career-best nine-under 63 at the links-style Senator course at the Robert Trent Jones Golf Trail’s Capitol Hill complex.
Twelve months ago Thompson became the youngest winner on the LPGA Tour when she won the event by five strokes.
A year on, she bettered that championship-winning form with nine birdies in a bogey-free round to top the leaderboard after the first round.
“It feels really good getting a first round of 63 under my belt, but you just have to take it one shot at a time,” Thompson said. “Can’t get ahead of yourself in this game, so just going to hope to play like I did today for the next three rounds.”
Lizette Salas and Hee Young Park shot 65s to share second while Stacy Lewis, Karen Stupples, Amanda Blumenherst, Wendy Ward and Mi Hyang Lee were three strokes off the pace.
World number one Yani Tseng was eight strokes back at 71, along with Michelle Wie.