The 22-year-old had looked set to take the first major of the season at the ANA Inspiration last month, before a rules breach cost her victory.
Thompson was was given a four-stroke penalty when a TV viewer spotted an infringement and emailed officials.
But she carded a final round 65 in Virginia to take a five-shot victory.
In Gee Chun of South Korea earned her third runner-up finish of the season with a bogey-free 67 on Sunday.
Thompson, ranked fifth in the world, started her final round three shots ahead of the field and recorded six birdies to card a record 264 for the tournament.
It was her first victory on the LPGA Tour since a 2016 victory in Thailand.
Meanwhile New Zealand's Lydia Ko held on to her world number one ranking despite a disappointing final day as a two-over par 73 left her in a four-way tie for 10th.
American Lexi Thompson earned her first victory of the year with a tournament record 20-under-par score at the LPGA Kingsmill Championship in Virginia.