Spain's Nadal breezed past countryman Daniel Gimeno-Traver 6-3, 7-5 at Jockey Club Brasileiro.
Meanwhile, Ferrer continued to roll two days after claiming the Copa Claro in Buenos Aires with a 6-2, 6-3 decision over Frenchman Jeremy Chardy.
No. 3 seed Fabio Fognini of Italy also advanced, shaking off Slovenian qualifier Aljaz Bedene 7-6 (7-5), 0-6, 6-1.
Fourth-seeded Tommy Robredo had an easier time of it, dispatching fellow Spaniard Pablo Carreno Busta 7-6 (7-5), 6-3, but fifth-seeded Nicolas Almagro of Spain was a surprise loser, falling to Ukrainian Alexandr Dolgopolov 2-6, 6-3, 6-0.
No. 6 seed Marcel Granollers also went down in an upset, dropping a 2-6, 6-3, 7-5 verdict to Portugal's Joao Sousa.