Tsitsipas has beaten the best player in the world to reach the Shanghai Masters semi-finals, as well as qualifying for the ATP Tour finals.
The 38-year-old Swiss now faces Alexander Zverev after the German came through 6-0 7-6 (4) against Russian opponent Andrey Rublev.
Daniil Medvedev's 6-3 7-6 (7-4) victory over Fabio Fognini sealed Tsitsipas' spot in the season-ending tournament in London for the first time and the 21-year-old capped a memorable Friday by beating Djokovic 3-6 7-5 6-3.
Djokovic sits at the top of the rankings at the moment but trails Rafa Nadal in the yearly standings and, with the Spaniard absent from Shanghai, had hoped to make up significant ground in China.
Zverev leads an imposing 4-0 head-to-head record with Daniil Medvedev, all of which were played on hard courts, but the he has not faced the world number four since the Rogers Cup past year and Medvedev is a wholly different proposition now.
"I don't know if I'm going to be able to beat him the next time or the time after that one, but I know there's going to be a time where I'm going to find opportunities and beat him".
Former Congressman Gowdy joins Trump legal team to fight impeachment move
Gowdy also might have been unwittingly auditioning for the job through his commentary on Fox News, the channel Trump favors. In addition to his gig on Fox, Gowdy works for the law and lobbying firm Nelson Mullins Riley & Scarborough of SC .
Gurley doubtful, Talib out vs. 49ers
Here are the biggest causes for concern facing Los Angeles this weekend as Sean McVay's team takes on one of its biggest rivals. The Rams on Friday listed star running back Todd Gurley as doubtful for their Week 6 game with the 49ers.
New Study Suggests Owning a Dog Could Add Years to Your Life
Caroline Kramer, assistant professor of medicine at the University of Toronto and an endocrinologist in NY . Their results show even greater benefit to the dog owners.
Medvedev took a tense and nervy opening set on a tie-break and broke early in the second to seize control of the contest.
Matteo Berrettini is up next for Zverev, who reflected on a remarkable end to the second set, when he was on the brink of a far more straightforward success.
The young Greek proved to be too strong for Djokovic, overcoming a slow start and playing against only one break point in the entire encounter to mount the pressure on the Serb who couldn't endure it, losing 3-6, 7-5, 6-3 in just over two hours to end his run in the quarters and get some well-deserved rest.
"I don't mean to be rude at all, but it's just boring".
Zverev, who will seek a 4th Masters title, has won all four meetings with Medvedev. "I take a lot of positives from this into the final tomorrow".
Prior to Friday's match, Fognini said Medvedev was one of the most risky players to face. Later, in response to a different query he said, "The crowds were unreal, they were going for it". "He was the better player in the second and third sets".
"He's definitely playing the best tennis of his life".