After reaching the Melbourne Park final eight for the first time, de Minaur was attempting to reach his maiden semi-final at any slam.
The world No.8 was chasing his first win over Sinner in 10 attempts, after winning just one set against the Italian in their previous nine meetings.
But defending Open champion Sinner outgunned, then dismantled the Australian to claim a straight-sets 6-3 6-2 6-1 win in just an hour and 48 minutes on Rod Laver Arena.
A shell-shocked Alex de Minaur went down in three quick sets to world No.1 Jannik Sinner. (James Ross/AAP PHOTOS)
Scintillating Sinner, 23, will face world No.20 Ben Shelton in the semi-final, after the American beat Lorenzo Sonego in Wednesday's other quarter-final.
"I feel like today I was feeling everything," Sinner said.
"When days (are) like this and you break quite early in each set, it's a little bit easier.
"He's a tough competitor. He's an amazing player.
Jannik Sinner came prepared for de Minaur and was delighted with his game. (Joel Carrett/AAP PHOTOS)
"We know each other quite well now. We played last year so many times and we try to understand each other's game, try to prepare ourselves in the best possible way.
"This kind of match, they can go quickly but also they can change very fast. If I go down with the level of it, he takes the opportunity.
"I'm very happy about my performance today."
The world No.1 has maintained his title defence despite having a doping saga hanging over his head, with a Court of Arbitration for Sport hearing set for April.
The World Anti-Doping Agency appealed against the decision not to ban the Italian after he tested positive twice for the anabolic steroid clostebol last March.
World No.2 Alexander Zverev and 10-time champion Novak Djokovic face off in the other semi-final.
But renowned workhorse de Minaur, 25, will have to lick his wounds and contemplate how he can take his game up another gear.
De Minaur had no answers as the world No.1 continued his dominance over him. (Joel Carrett/AAP PHOTOS)
He has now failed to claim a set in his four quarter-final appearances at slams to date.
De Minaur had dropped just one set across the opening four rounds at Melbourne Park but quickly fell behind against Sinner, who showed no signs of the illness that plagued his fourth-round win over Holger Rune.
Sinner seized the early edge when he broke de Minaur in just his second service game to take a 3-1 lead before wrapping up the opening set.
Sinner picked up where he left off, breaking de Minaur's serve in the opening game of the second set, then saving a break point himself.
He broke de Minaur again to tighten his grip on the second set, before claiming it.
The third set proved a formality with Sinner again breaking de Minaur in the first game and racing to a 4-0 lead before sealing victory.
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