The 22-time Olympic medalist delivered his second dazzling performance in as many days as he blitzed the field with a time of 50.45 seconds, on day three of the nationals.
He also eclipsed the 50.56 time that South African Chad le Clos posted in winning the 100m butterfly at the world championships some eight hours earlier in Kazan, Russia.
Le Clos had marked that victory by aiming some pointed verbal barbs at Phelps -- who is swimming in San Antonio this week rather than in Kazan because his drunk-driving arrest in September cost him his world championships berth.
"I absolutely love it," said Phelps, whose 18 Olympic golds include his incredible eight in Beijing in 2008. "It just fuels me. Whatever I do in the pool will speak for itself."
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Phelps's 100m fly time was also almost a second faster than his gold-medal winning performance at the 2012 London Olympics.
"I think that is exactly where I want to be right now," said Phelps, who set the world record of 49.82 in Rome in 2009. "Let that swim make statements."
Phelps easily beat runner-up Jack Conger, who finished in 51.33, while David Nolan was third in 52.15.
It was faster than the 1:52.96 Le Clos swam to beat Phelps at the London Olympics and faster than Hungarian Laszlo Cseh's 1:53.48 to win the world title in Kazan this week.
Exactly how much progress Phelps was making in his comeback was a bit of a mystery coming into the US meet, thanks to the suspension he served for the DUI and the fact that he hadn't tapered his training to produce his fastest times in any meeting this year.