Nadal, seeking his fourth consecutive Paris victory, improved to 55-1 all-time at Roland Garros with the 7-6 (7-5), 6-4, 6-4 decision over Fabio Fognini in sunny and breezy conditions.
The Spanish star will next face 13th-seeded Kei Nishikori of Japan, who eliminated 24th-seeded Frenchman Benoit Paire 6-3, 6-7 (3-7), 6-4, 6-1 to become the first Japanese man to reach the fourth round at the French since 1938.
Djokovic downed 26th-seeded Bulgarian Grigor Dimitrov 6-2, 6-2, 6-3 in a 1-hour, 44-minute match. Next up for him will be sixth-seeded Philipp Kohlschreiber of Germany, who breezed past Romanian Victor Hanescu 6-0, 7-6 (7-0), 6-1.
Also logging victories Saturday were No. 7 Richard Gasquet of France, who dispatched Russian Nikolay Davydenko 6-4, 6-4, 6-3, and No. 29 seed Mikhail Youzhny of Russia, who sent eighth-seeded Serb Janko Tipsarevic packing by a 6-4, 6-4, 6-3 margin.
Ninth-seeded Stanislas Wawrinka moved on as well, with a 6-3, 6-7 (2-7), 6-3, 6-3 decision over 21st-seeded Pole Jerzy Janowicz.