Tsitsipas faced two match points before the in-form Greek teenager stunned Zverev in Toronto.
World No.1 Nadal stopped red-hot No.6 seed Cilic to book his spot in the final four at the ATP 1000 tournament.
But there is just no stopping Tsitsipas after the 19-year-old ousted No.2 seed Zverev 3-6 7-6 (13-11) 6-4.
Tsitsipas came from 6-3 and 5-2 down to shock Zverev in his first ATP 1000 semi-final.
He also became the youngest player since Nadal in 2006 to beat three top-10 players in a single tournament, having defeated Zverev, Novak Djokovic and Dominic Thiem en route to the final four.
"Achieving such things makes me feel nice," Tsitsipas said.
"I'm very proud of who I am and at this age to have these kind of results, which I never expected. I always thought it's going to be take more years for this to happen. But with the hard work that I've been doing, it's no surprise to me. I believe I have the game to compete against these players. I'm feeling very confident."
It does not get any easier with world No.6 Kevin Anderson awaiting in the semi-finals.
Meanwhile Nadal, the 17-time grand slam champion, battled to a 2-6 6-4 6-4 win over Australian Open runner-up Cilic.
Nadal was overpowered and outplayed in the opening set as Cilic looked set to advance to the last four.
That was before Nadal — seeking his 33rd title — stood tall to survive as the Spanish star became the first singles player to secure his spot at the ATP Finals in London.
"It means a lot to me to be in the semi-finals," Nadal said.
"It's because it was a very important match for me. Being in the semi-finals is great news at the start of the hard court season. And winning three good matches in the first Masters 1000 is so important for me."
A three-time Canadian champion, Nadal will face Karen Khachanov after the Russian accounted for Robin Haase 6-3 6-1.
No.4 seed Anderson, from South Africa, overcame a poor head-to-head record to move past Grigor Dimitrov 6-2 6-2.
Wimbledon finalist Anderson had lost six of his seven meetings against No.5 seed Dimitrov before this latest victory.
"I felt I played really well right from the beginning," Anderson said.
"I think I played some really good tennis in the last couple of matches, just not from the start... I felt I was in a really good frame of mind, playing the kind of tennis that I knew I wanted to be playing and needed to be playing."