The world No5 had looked dead and buried as he quickly fell well behind but remained undeterred by the fact that Nadal had lost just once in his Grand Slam career when leading by two sets.
Aptly perhaps, the only time had come against Fabio Fognini at the 2015 US Open, a player Nadal had beaten in straight sets in the previous round only two days ago.
But Tsitsipas showed tremendous resolve to produce a coming-of-age performance on Rod Laver Arena. Before Wednesday’s quarter-final, he had beaten just one top-10 player at a Grand Slam, Roger Federer at the same venue.
Tsitsipas, who looked fresh throughout, perhaps buoyed by a walkover against Matteo Berrettini in the previous round, said afterwards: “I have no words to describe what just happened out on court. It’s an unbelievable feeling to be able to fight at such a level and give it my all out on the court. I don’t know what happened.”
Nadal showed little sign of the back injury which had curtailed his preparation and raced into a 6-3 6-2 lead, taking his streak of consecutive Grand Slam sets won to 35.
But his hopes of equalling Roger Federer’s 2007 record of 36 were derailed by Tsitsipas.
The Greek raised the quality of his tennis in the third set, forcing a tiebreak despite the fact Nadal had won 27 of 28 points on his serve before then.
In it, Nadal’s game suddenly cracked, the Spaniard taking his unforced errors for the set up to 11 in contrast to the more clinical Tsitsipas.
It gave him a timely confidence boost, the 22-year-old showing a swagger between points as he adapted his approach to make Nadal play more and bring out unforced errors from the other side of the net as the fourth set dragged out.
Such tactics delivered his first break of the match with the scores level at 4-4 and he made no mistake in serving out the set to force a decider.
The momentum appeared to shift towards Nadal for a time as he served first, until Tsitsipas conjured up three break points with the scores at 5-5, converting the first when Nadal sent the ball wide. It left him with the opportunity to serve out the match, which he duly did.
In three previous encounters between the pair, Medvedev had not dropped a single set and, although set one was close, Medvedev edging it appeared to extinguish the fire in Rublev.
The younger of the two Muscovites by two years, Rublev, increasingly struggled with the heat and humidity on one of the hottest days at this year’s tournament, which increasingly zapped any sort of fight out of the 23-year-old.
As he slumped over in between points, Medvedev steadily imposed his stranglehold for a 7-5, 6-3, 6-2 victory.