The first-seeded Ferrer of Spain, a three-time champion at the Abierto Mexicano, trounced lucky loser Antonio Veic of Croatia 6-0, 6-3 in a match in which Ferrer won 4-of-5 break points.
Second-seeded Nadal, also representing Spain, ousted Argentine qualifier Diego Sebastian Schwartzman 6-2, 6-2 in his first appearance in Acapulco since winning the tournament in 2005. Nadal is seeking his 38th clay-court championship.
Fellow Spaniard and No. 3 seed Nicolas Almagro won his 300th career match with a 6-0, 6-1 thrashing of Mexican wild card Cesar Ramirez.
Also advancing Tuesday were eighth-seeded Horacio Zeballos of Argentina and Wayne Odesnik of the United States. Odesnik topped Poland's Lukasz Kubot 6-3, 6-4 and will face Ferrer in the second round.