Australian tennis's great men's hope was sent crashing on Friday by the Greek superstar, who rolled back the glory years to inflict a 6-3 7-6 (7-3) victory in the second round.
Setting aside the injury woes that has curtailed his career, the one-time world No.3 disposed of de Minaur in one hour and 41 minutes.
De Minaur's head to head record with world No.51 Tsitsipas makes for interesting reading.
In their 16 meetings dating back to 2017, the world No.6 has won just twice - in first-round qualifying on grass at Surbiton in 2017 and in the quarter-finals of Acapulco in 2024.
De Minaur made it a closer contest on Friday (Saturday AEDT) than their head-to-head record suggests.
Tsitsipas hurled down five aces to de Minaur's two and won a whopping 98 per cent of his points on first serve, but could only muster one break-point opportunity.
But it was all he needed, as de Minaur failed to convert two of his chances.
Tsitsipas will now meet No.28 seed Arthur Fils for a place in the last 16.
Earlier, Australian qualifier Adam Walton dished out eight aces in a 6-2 6-2 first-round win over Argentine Sebastian Baz.
Apart from a heap of ranking points in an ATP 1000 Masters event, his reward is a meeting with No.12 seed Jakub Mensik in the round of 64.
Missing out though was compatriot Chris O' Connell who put up a brave fight before losing to Hungarian Marton Fucsovics 7-6 (8-6) 6-3.
Top-seed Carlos Alcaraz was a 6-4 6-4 winner over Joao Fonseca and Ethan Quinn upset No.11 seed Casper Ruud 6-4 7-6 (9-7).
Jack Draper was beaten by big-serving Reilly Opelka 7-6 (7-3) 7-6 (7-0), and Italy's Matteo Berrettini, a former world No.6, clinched a surprise 6-4 6-4 win over No.10 seed Alexander Bublik.
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