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.
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 previous year and Medvedev is a wholly different proposition now.
"I knew if I keep playing the way I was playing in the first two sets I was going to have a chance in the third as well".
The history was with Medvedev but there was nothing in it as he and Tsitsipas entered the first-set tie break after 43 minutes of high-quality tennis.
Tsitsipas, who stunned Novak Djokovic a day earlier, falls to 0-5 against Medvedev.
Four-time champion Djokovic was denied back-to-back titles after his Japan Open Tennis Championships triumph last weekend as Tsitsipas struck 34 winners in a pulsating quarter-final in Shanghai, setting up a last-four contest with Medvedev.
"I don't mean to be rude at all, but it's just boring". I felt like I've played some decent tennis this week and being in a Masters 1000 final here in Shanghai is also something very special for me. Medvedev in particular has won more matches than anybody, and reached his first Grand Slam final at the US Open, requiring Rafael Nadal to take the decider before eventually putting him down.
The Italian, 13th in the world, put up a better fight in the second set but was broken in the ninth game as his hopes of an upset faded. Hard court data this year shows the duo having nearly identical service points won numbers, but Medvedev winning nearly 7% more return points - a huge advantage - and given that he's had historical success against Tsitsipas in their previous meetings, all of which are from 2018 onwards, there's a strong case to suggest he's value for a small stake at market lines.
"He's different this year", Zverev said.
In an interview with AFP last month in Zhuhai, southern China, the world number seven gave an insight into the mindset which propelled him to those victories.