Popyrin is drawing on the memories of his seismic victory over Novak Djokovic last year in New York after setting up a second-round blockbuster with the top-seeded Sinner.
Popyrin immediately turned his attention to taking on the defending champion and world No.1 after blasting 10 aces and 44 winners to see off Finland's Emil Ruusuvuori 6-3 6-4 7-6 (7-3) in just over two hours on Tuesday (Wednesday AEST).
"Jannik's the best in the world and is one of the best for a reason, but I don't feel too starstruck by the occasion," the 26-year-old said.
"I've been in that position before. Last year is a great example of it.
"If I can stick to my game, if I can play the way that I want to play, then I can cause trouble."
Djokovic is far from the only big scalp Popyrin has claimed.
The former French Open junior champion has a history of bringing down top-10 stars, most recently this month when he ousted world No.9 Holger Rune during his Canadian Open title defence.
"I've walked out on to Arthur Ashe Stadium before, so I know what to expect," Popyrin said.
"Walking out against Novak, it was a little bit different because I played him on two previous occasions that year, and all in slams.
"But you're playing one of the top guys in the sport and they're the moments that I relish.
"They're the moments where I come out and play some of my best tennis, and I'm hoping that I can do that again."
Popyrin boasts a rare head-to-head winning record over Sinner, having beaten the Italian in their only previous meeting, on clay at the 2021 Madrid Masters.
While unwilling to share, the Australian No.2 is convinced he has the game plan to topple Sinner.
"There's a game plan to beat everybody," he said.
"Based on my past experiences against him, based off when I played against him in January (in an exhibition), I picked up a few things and I've got a pretty good memory when it comes to playing against players.
"I feel like if I play them once, I know what to expect from them next time.
"So in a way it was lucky for me to play him this year in January. I have a game plan, and I think everybody has some sort of weakness."
Brushing aside any concerns about the illness that had derailed him in the Cincinnati Open final eight days earlier, Sinner was typically merciless in opening his quest for a fifth career major, needing just 98 minutes to dispatch Czech world No.89 Vit Kopriva 6-1 6-1 6-2.
World No.3 Alexander Zverev, eighth seed Alex de Minaur and 14th seed Tommy Paul also safely progressed to round two.But there was no joy for 2014 US Open winner Marin Cilic, with 23rd seed Alexander Bublik scoring a 6-4 6-1 6-4 win over the 36-year-old Croat.
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