Top seed Djokovic carved out a 4-6 6-3 6-4 6-4 win over 16th seed Philipp Kohlschreiber yesterday, with the German paying a high price for converting just two of 13 break points.
World number one Djokovic goes on to face German 35-year-old Tommy Haas, who became the third oldest man to reach the last-eight with a comfortable 6-1 6-1 6-3 win over volatile Russian Mikhail Youzhny.
Nadal, bidding to become the first man to win the same Grand Slam title eight times, trounced Japanese 13th seed Kei Nishikori 6-4 6-1 6-3.
The defending champion next faces Swiss ninth seed Stanislas Wawrinka who reached his first French Open quarter-final, beating French seventh seed Richard Gasquet, 6-7 (5/7) 4-6 6-4 7-5 8-6.
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"I needed to earn my victory, and in the end it was good. I'm really glad to get through, because he's a good quality opponent and he's a specialist for this surface," said Djokovic of Kohlschreiber.
On facing 12th-seeded Haas, against whom he has a 4-3 winning record, the Serb said: "I have a lot of respect for Tommy. He is playing well."
The last time he failed to reach the last-eight of a major was in Paris in 2009 when he lost in the fourth round to Monday's opponent.
Nadal arrived in Paris having collected six titles in eight finals since his return from a seven-month injury lay-off.