The 22-year-old took the lead early and never gave her opponents a chance, clinching her spot in the world championships in front of an adoring crowd.
"I was just gonna finish the race, knew anything was possible," she said.
Britton Wilson finished 1.67 seconds behind with Shamier Little taking third in 53.92.
McLaughlin previously set the record with a 51.90-seconds performance at the U.S. Olympic trials a year ago, only to shatter that figure in Tokyo, collecting gold in 51.46.
She faces a potential showdown at worlds with chief rival and reigning champion Dalilah Muhammad, who was absent from the national championships due to injury.
The top three finishers in Eugene, Oregon, who meet certain qualifying standards, and reigning global title-holders will compete at the world championships, which will be held in the United States for the first time from July 15 at the same track.
Photo: SEAN M. HAFFEY Caption: Sydney McLaughlin