McLaughlin polished the record from the Olympics in Tokyo last year by five hundredths, the new record is 51.41.
The championships also serve as a qualifier for the World Cup, which will be held at the same arena in Eugene later this summer.
"Every time I come here, I just feel that something fantastic will happen," McLaughlin said after the race, according to Reuters.
She also set a world record in the same arena a year ago when there were also national championships before the Olympics.
Can not compare with the first time
- I can not compare with the first time you do it, just that it was so reverent to cross the finish line, says McLaughlin who sticks to vegetarian food.
- But now I will celebrate by eating real food, she says.
Second in the race was Britton Wilson who had 53.92 - 1.67 seconds behind McLauglin.
Countryman Dalilah Muhammad was over the race due to a minor injury.
At the last World Cup, 2019 in Doha, Qatar, Muhammad won before McLaughlin in second place.
As the reigning world champion, Muhammad has a wildcard to the World Cup in three weeks.
The World Athletics Championships were planned to be held last year but were postponed because the last Summer Olympics were postponed for a year due to the pandemic.