The seven-time French Open winner is making a comeback after being away from the tour for more than seven months with a left-knee injury.
Nadal made the final of the VTR Open earlier this month in Chile before losing to Argentine Horacio Zeballos. A week later he reached the final of the Brazil Open and defeated David Nalbandian to secure the title.
He is seeded No. 2 in the clay court tournament at Mexico, behind fellow Spaniard David Ferrer.
Ferrer also won his first-round match on Tuesday, defeating Antonio Veic 6-0, 6-3. Ferrer is the three-time defending champion and won last week in Buenos Aires, his second title of the season.
No. 3 seed Nicolas Almagro of Spain defeated Cesar Ramirez of Mexico 6-0, 6-1.
Nadal rested last week, giving his left knee a chance to heal. He has said the knee still hurts and has been told he has to live with it until the pain slowly goes away.
No. 4 seed Stanislas Wawrinka was upset by Fabio Fognini 6-2, 7-6 (3).
On the women's side of the combined ATP-WTA tournament, top-seeded and defending champion Sara Errani of Italy defeated Alexandra Cadantu of Romania 6-3, 6-2.