Sixth seed Tsitsipas battled back from a set down to defeat top seed Djokovic 3-6 7-5 6-3 to register his first victory over a reigning world number one.
The 38-year-old Swiss now faces Alexander Zverev after the German came through 6-0 7-6 (4) against Russian opponent Andrey Rublev. "But I want to keep the momentum going and hope I can make it to seven or eight".
The 23-year-old edged the first set thanks to two-straight errors from Tsitsipas in the tie-break.
Seventh-ranked Tsitsipas blinked first, gifting set point when he shanked a forehand and then doing the same moments later to put the fourth-ranked Russian a set up.
In the second round, Novak took down Denis Shapovalov 6-3, 6-3 in 70 minutes, dropping eight points on serve and taking nearly half of the return points to dominate all the time, breaking Denis three times and moving over the top to set the third-round clash with John Isner.
"It's a great achievement, I'm proud of myself and, hopefully, I get the win tomorrow", said Medvedev.
"I don't mean to be rude at all, but it's just boring".
"I was close to losing a lot of them but I think that's also the confidence and dynamic that I'm going through".
Federer has also won 28 Masters 1000 titles in his illustrious career. "He was the better player in the second and third sets".
But following his match, the Russian was surprised to learn that he still has a ways to go to catch two of those men: Roger Federer and Novak Djokovic.
Zverev took his opportunities in the final set and finished the encounter with 43 winners to Federer's 21. Zverev may feel that, now that he has beaten Federer, the hard work is done, but the Italian has already proved his ability to handle the big occasion numerous times this year.
The words "crazy", "amazing" and "dangerous" have been used by current and former tennis players to describe Daniil Medvedev this week, with at least two of them considering the Russian to be the most unsafe player so far. "He's been playing some unbelievable tennis in the last few months".