Nadal, the world No. 1 who has taken the Monte Carlo title six consecutive years, handled 13th-seeded Richard Gasquet of France 6-2, 6-4.
Nadal shook off the unseasonable cold and won his 34th straight match at Monte Carlo Country Club to advance to the quarterfinals against unseeded Croat Ivan Ljubicic, who bumped off fifth-seeded Tomas Berdych of the Czech Republic 6-4, 6-2.
Second-seeded Federer moved on with a 6-4, 6-3 win over 15th-seeded Marin Cilic of Croatia. He'll next face seventh-seeded Austrian Jurgen Melzer, who posted a 6-1, 6-4 decision over ninth-seeded Spaniard Nicolas Almagro.
No. 3 Andy Murray downed 16th-seeded Frenchman Gilles Simon 6-3, 6-3 and advanced to play Portuguese qualifier Frederico Gil, who bounced eighth-seeded Frenchman Gael Monfils 7-6 (8-6), 6-2.
Also Thursday, fourth-seeded Spaniard David Ferrer dispatched Canadian Milos Raonic 6-1, 6-3, and 11th-seeded Serb Viktor Troicki prevailed when Tommy Robredo retired with a left adductor injury while leading 6-3, 1-2.