Nine-times champion Nadal had fitfully found some form after a horror opening four games against the rampant Djokovic, whose previous six encounters with the Spaniard at Roland Garros had all ended in despair, twice in the final.
For a while, something seemed to have stirred inside Nadal, the old timing sending the ball hurtling to within inches of the opposite baseline. For a while Djokovic doubted.
Yet once a hesitant Nadal plopped a volley into the tramlines to hand Djokovic the opener on his sixth set point, there was an inevitability about the outcome of the 44th meeting between the two players.
Commentating on the match for Eurosport, former world number one John McEnroe said Nadal seemed to be playing with “weights on his ankles” in the early stages.
The only thing holding Djokovic back was self-belief — not usually an ingredient missing from a player who has been virtually unbeatable this year.
There was panic in his eyes when he surrendered that 4-0 lead, old scars re-opening.
However with the opening set in his pocket, Djokovic turned up the heat to leave Nadal in uncharted territory, having never lost the opening two sets at Roland Garros since his debut in 2005.
Nadal’s seemingly bottomless tank of fighting spirit has fuelled a career that has brought him 14 grand slam titles, but even that precious commodity ebbed away on Wednesday.
His 39-match winning streak at Roland Garros ended in feeble fashion, with a double-fault not one of the mind-boggling rallies the two gladiators have produced down the years.
“As I said every year when I won here, the only thing that makes me happy is have the trophy with me,” Nadal, who was ‘celebrating’ his 29th birthday told reporters.
It would be foolish to suggest the greatest claycourt player ever to slide on dirt cannot come back and reclaim his title next year, but his aura of invincibility is fading fast.
“I am happy the way that I recovered my level the last month, but probably not enough yet to play against and to win against Novak. I competed, but not to win,” he said.
“I’m gonna fight. I lost in 2009 and was not the end. I lost in 2015, and is not the end. I will do my best to be back to win. I will do my utmost to have more wins.”
Nadal’s record at Roland Garros now stands at 70-2.
But this defeat felt different to the one he suffered at the hands of Sweden’s Robin Soderling in 2009.
Then, as was proved weeks later when creaking knees forced him to surrender his Wimbledon crown without striking a ball in anger, he was clearly struggling with his physical condition.
Against Djokovic on Wednesday, he simply looked like a player whose almost superhuman powers are on the wane while Djokovic is at the pinnacle of his career.
Nadal’s forehand, the leitmotif for his stellar career, now lacked venom, his movement seemed a split second slower and his thinking became befuddled at pressure moments, like when he missed an easy smash at 30-15 ahead in the 12th game of the first set.
Djokovic on the other hand looked like a man bent on completing his career grand slam in a few days time, although Britain’s Andy Murray still provides a daunting semi-final barrier.
Murray, though, had better not look too closely at the stats.
Djokovic began the year by beating the Scot to claim a fifth Australian Open, completed a rare “double” at Indian Wells and Miami and is unbeaten in slams and Masters 1000 tournaments since last October. He looks invincible.
He knows, however, that no silverware is handed out for winning quarter-finals — even if this one felt like a final.
“Obviously an ideal scenario is today could have been finals and could have a different discussion,” he said. “Right now I’m aware that this is a big win, which I will enjoy tonight.
“But tomorrow is a new day and I have to move on. I want to fight for the title. That’s what I came here for.”
(Reporting by Martyn Herman in London; Editing by Douglas Beattie)