Thompson, at age 16, would become the youngest winner in the history of the circuit. She led this event in 2009 as a 14-year-old amateur before finishing 27th.
After starting the second round one shot out of the lead, Thompson posted a 4-under-par 68 at the Capitol Hill course on the Robert Trent Jones Golf Trail and her 36-hole total of 134 gave her a two-shot advantage over Stacy Lewis and Becky Morgan.
The LPGA Tour has an age limit of 18 for full-time membership, but because of her proven skills Thompson has been granted permission to go through the qualifying tournaments later this year.
Marlene Hagge holds the LPGA Tour record for youngest winner, having captured the 1952 Sarasota Open at the age of 18 years, 14 days. She won another tournament two months later and went on to become one of the most famous players in women's golf.
World No. 1 Yani Tseng stumbled to a 73 Friday and was tied for 23rd at 141.