"I wanted to get under 52," Phelps told reporters.
"I was sick and tired of seeing 52.1."
He easily beat his times in the event from his previous three meets but still has work to do to match his 51.21 winning time from the 2012 London Games.
"I am very pleased with being able to go 51," he added.
"But in the grand scheme of things, I think it's just a small stepping stone to go where we hope to be.
"I always set high expectations for myself, no matter what I'm doing.
“(Coach) Bob (Bowman) and I have a plan of what I want to do. He knows what it's going to take to get there."
Only Russian Vyacheslarus Prudnikov (51.60) has been faster this year.
Lochte was second in 53.08 with Matthew Josa third in 53.64.
Lochte was victor in the only other meeting between he and Phelps this year, but is on his own comeback trail after aggravating a knee injury in April.
The 'Bulldog Grand Slam' continues in Athens on Saturday with Phelps scheduled to swim the 100m backstroke as he prepares for the Aug. 6-10 U.S. Championships in Irvine, California ahead of the Pan Pacific Championships on the Gold Coast in Australia.
(Reporting by Ben Everill; Editing by Ian Ransom)
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