Cilic, the 2014 champion, may have been justified in expecting an easier pathway past the third round, but the 19-year-old De Minaur has already earned a reputation for having an abundance of fighting spirit in his relatively short career.
Where his compatriot Nick Kyrgios slumped to a tame loss at the hands of Roger Federer earlier in the day, De Minaur started on the front foot, running down everything Cilic sent over the net to carve out a 2-0 lead.
Cilic rallied behind his big serve but De Minaur made the Croatian work hard for every point all the way to the bitter end at 2.22 a.m. local time (0622 GMT), only a few minutes short of the latest ever finish at the U.S. Open.
"Incredibly happy, it was just an insane atmosphere," Cilic said on the Louis Armstrong Stadium court after setting up a last 16 meeting with David Goffin.
"Incredible fighting spirit. He played some amazing tennis. I was just a little bit luckier today.
"It doesn't get any better. What time is it? Two-thirty in the morning and everybody staying around? To come from two sets down, it's one of the best matches in my career."
Trailing 5-2 in the final set and serving to stay alive, De Minaur staved off five match points to force Cilic to win the match on his own serve, and then saved another before breaking the Croatian and bringing the score to 5-4.
He held on to level at 5-5 before Cilic held to love and broke again to seal the match on his eighth match point in three hours and 59 minutes.
Cilic hit 14 aces to De Minaur's four but the Croatian, who won 73 percent of his first serves, was undermined by inconsistency, making 70 unforced errors.
Both players were neck-and-neck from the baseline, but De Minaur's gritty performance was well reflected by the fact that he saved 20 of the 28 break points he faced.
In the end the crowd were firmly on the fresh-faced youngster's side, willing him on to victory and giving him a standing ovation as he walked off the court in defeat at the end of the epic contest.
(Editing by Nick Mulvenney)
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