Djokovic and Nadal met in the semi-final of the competition last year, which saw the Serb emerge victorious after an epic battle.
Nadal came into the French Open with little experience on clay, having only played five matches on the surface this year.
Djokovic was aiming to keep his perfect record against the Argentine, but as he went out of the tunnel onto the court, he discovered that not was on the same page.
The King of Clay advanced to the quarter-final where he will face world no. 1 Novak Djokovic, who beat Diego Schwartzman in straight-sets.
The match ended with Hugo Gaston recording an unlikely victory over Alex de Minaur by a score-line of 4-6, 6-2, 6-3, 0-6, 7-6 (10-4).
With form and confidence on his side, it looks like the 34-year-old is the man to beat for the highly anticipated tournament in the French capital.
As Novak Djokovic beat Stefanos Tsitsipas in the final of the Italian Open, his son, Stefan, won a club competition in Serbia.
The Norwegian Ruud came out as the victor after what was a thrilling contest that saw a brilliant tie-break in the very first set.
Day six saw third seed Rafael Nadal eliminated by Canada's Denis Shapovalov who recorded a fantastic comeback win.
After beating second seed Alexander Zverev 6-3, 6-1, the 19-year-old mentioned that it was watching Rafa win this particular title as he was growing up that inspired him.