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|Stefanos Tsitsipas on his way to victory over Novak Djokovic. (AFP/Vaughn Ridley)|
The Greek teenager, who turns 20 on Sunday, followed up his defeat of seventh seed Dominic Thiem, beating four-time champion Djokovic, seeded ninth, in a first-time meeting.
"This was the best match of my career," Tsitsipas said. "I knew I was playing pretty good today.
"Losing the second set, it was tough to deal with - I had my opportunities and didn't use them.
"But I remained calm, I tried few things that I didn't try before. (The early break in the third set) was everything. It gave me the win at the end."
Tsitsipas, ranked 27, spent just over two hours in advancing to the first Masters 1000 quarter-final of his career.
The 19-year-old forced the former world number one Djokovic onto the back foot in the first set but was unable to wrap up a straight-sets win as the 13-time Grand Slam champion claimed the tiebreak with the Greek firing long having saved two set points.
In the third set, the teenager showed great composure to break for a 2-0 lead and then saved a break point for a 3-0 margin.
He rounded off his afternoon with back-to-back winners to send Djokovic, the winner of 30 Masters titles, out on a first match point.
He played very well and deserved to win without a doubt," Djokovic said. "I just played not that great.
"I didn't return well. It wasn't that great of a match."
Upset scenarios were not in the plan of holder Alexander Zverev, who rolled over Russian Daniil Medvedev 6-3, 6-2 in just 52 minutes while never facing a break point.
Bulgarian fifth seed Grigor Dimitrov required almost two and a half hours to subdue Frances Tiafoe of the United States 7-6 (7/1), 3-6, 7-6 (7/4).
He next faces Wimbledon runner-up and fourth seed Kevin Anderson who defeated Ilya Ivashka of Belarus 7-5, 6-3 to also make the last-eight.
"It's great, I haven't competed in about four and a half weeks. And to come out and just play, I mean, that's all I wanted," said ATP World Tour Finals champion Dimitrov.
"I was really not focusing on winning or losing, just on starting to play good tennis and start building the right habits."
Dimitrov, who last reached a quarter-final in April, added: "Clearly I'm not playing my best tennis, but I'm finding a way and managing to go through those matches.
"I think I'm improving. With each game, with each point that I play, I feel more confident, more stable on the court, and everything falls into its place."
Sixth seed Marin Cilic continued his quiet progress, beating Argentine 11th seed Diego Schwartzman 6-3, 6-2.