Nick Kyrgios, the Australian 31st seed, will begin his campaign after his first-round bye later on Sunday (AEDT) against veteran German Philipp Kohlschreiber.
De Minaur wasn’t the only seeded player to crash out in the second round as teenager Felix Auger-Aliassime stunned Stefanos Tsitsipas 6-4, 6-2 to record his first top-10 scalp.
The Canadian 18-year-old Auger-Aliassime claimed the first break to earn a 4-2 gap and that was enough to secure the opening set against the ninth seed.
Tsitsipas, who earned a top-10 ranking for the first time in his career after a strong start to the year, made a group of errors to fall behind in the second set.
An unfortunate net error from the 20-year-old Greek followed by a wild forehand conceded a break before Auger-Aliassime stretched further away as he fired down an ace to lead 3-1.
Auger-Aliassime unleashed a punishing backhand pass and ruthlessly rallied until Tsitsipas wilted to surrender another break, giving him the opportunity to serve for the match.
The world No. 58, who became the youngest player to reach an ATP 500 event final in Rio de Janeiro last month, showed no signs of nerves as he served out the biggest win of his young career.
“I was able to serve well and I felt aggressive, pretty solid,” Auger-Aliassime said.
“Mentally, I felt like I had the edge having beat him three times in juniors when we first met.
“I’m able to play well in the big points and the momentum I’m having gives me great confidence.”
Fifth-seeded Kevin Anderson withdrew from the tournament before his opening match of the tournament due to an elbow injury.
The South African’s misfortune proved a fill-up for lucky loser Miomir Kecmanovic who overcame Maximilian Marterer 6-3, 6-2 to move into the third round.
The 19-year-old Kecmanovic will play fellow Serb Lazlo Djere for a spot in the round of 16 after the wildcard eased past Guido Andreozzi 6-3, 6-4.