Australia's world No.13 dispatched Yibing Wu 6-1 6-2 6-1 in just 86 minutes to storm into the last 32 for the fifth time in seven trips to New York.
A quarter-finalist in 2020, de Minaur loves the faster pace of Flushing Meadows and sped through Thursday's match in vastly different fashion to his laborious four-set, first-round dogfight against Kazakh qualifier Timofey Skatov.
Wu is the Chinese giant-killer who not only dumped Nick Kyrgios out of Stuttgart in the grand slam finalist's premature return from a knee injury this year but also upended Denis Shapovalov and Taylor Fritz en route to the final on Dallas hard courts in February.
But de Minaur broke him seven times, won 82 per cent of his first-serve points and committed a meagre 10 unforced errors in 22 games to join countryman Rinky Hijikata in the last 32.
"Matches are never easy so whenever you get a chance to kind of come away with a win like that, you will take it for sure," de Minaur said.
"I don't think he was feeling 100 per cent today. It's a shame for him but ultimately it is one of those matches I did what I needed to do and happy to be in the next round.
"I was proud of my mental head space the whole match. I was locked in from the very first point until the last and no matter what was happening in the match.
"You always take a drama free match."
The 13th seed will play Nicolas Jarry next on Sunday (AEST) after the world No.25 ended the run of 17-year-old American wildcard Alex Michelsen 4-6 6-3 6-3 6-3.
De Minaur beat the Chilean in two tiebreakers in their only previous encounter at tour level, on a hard court in Acapulco four years ago.
He also needed two tiebreakers to see off Jarry in a lower-level encounter when the two first arrived in the pro ranks and knows dealing with the South American's huge serve will once again be key.
"He's dangerous because he's very big and has a great serve and forehand," de Minaur said.
"He's got very good weapons that at any moment he can just flip the switch and take the racquet our of your hand.
"It is going to be a difficult match in the sense that I am going to have to do my best to keep him on the run and uncomfortable out there and try to not to let him dictate to me."
De Minaur and wildcard Hijikata are the only remaining Australians left in the Open draw after Chris O'Connell succumbed 6-2 6-2 6-7 (6-8) 6-2 to third-seeded 2021 champion Daniil Medvedev in his second-round match.
Hijikata is up against China's world No.67 Zhizhen Zhang on Friday (Saturday AEST) in his first grand slam third-round appearance.
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