De Minaur, who made the last eight at Melbourne Park for the second time, was aiming to reach his first semi-final at any grand slam tournament.
The world No.6 was also chasing his first win over Alcaraz in six attempts.
But the Spanish superstar proved he remains a level above de Minaur in a 7-5 6-2 6-1 victory at Rod Laver Arena on Tuesday night.
De Minaur fought valiantly but was ultimately outclassed by Alcaraz, who is seeking to become the youngest man in the open era to complete a career grand slam.
The 22-year-old - already a six-time major winner - will next meet German world No.3 Alexander Zverev in his first AO semi-final.
"I'm just really happy with the way that I'm playing every match," Alcaraz said.
"Since the first round until now, I was increasing my level every match, which I'm just really happy about.
"I want all the things right now so after the first match (my team) told me, 'Be patient. The level you want to play is going to come for sure.'
"I think today I just feel really comfortable playing great tennis, which I'm really proud about, and I'm just really, really happy to get into a semi-final."
De Minaur, who was beaten by Jannik Sinner in the quarter-finals last year, was the last Australian left standing in the men's and women's singles draws.
The 26-year-old has now lost his first seven grand slam quarter-final appearances - the third man in the open era to do so, after Andrey Rublev and Tommy Robredo.
He traded blows with Alcaraz for 90 minutes before he was eclipsed.
"It doesn't feel amazing, I'll tell you that," de Minaur said.
"You try do the right things, you try keep on improving.
"But when the results don't come or the scoreline doesn't reflect those improvements, then of course you feel quite deflated."
In a red-hot opening, Alcaraz raced to a 3-0 first-set lead but was pegged back just as quickly.
Both players produced moments of brilliance - de Minaur's mid-air backhand winner was a highlight - before controversy arose at a crucial juncture in the set.
Alcaraz led 6-5 when de Minaur was handed a time violation while serving.
In a show of sportsmanship, the Spaniard defended his opponent to the chair umpire, declaring he wasn't ready to receive, but it was to no avail.
De Minaur won only six fewer points than Alcaraz in the second set (32-26) but couldn't match his opponent.
It appeared to knock the stuffing out of de Minaur as his hopes faded in the third set, before he waved farewell to adoring local fans for another year.
"You get back up, right? That's what it is," de Minaur said.
Earlier on Tuesday night, Australian pair Jason Kubler and Marc Polmans advanced to the men's doubles semi-finals with a 6-4 7-6 (7-3) win over French duo Sadio Doumbia and Fabien Reboul.
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