The world number one was rarely troubled by the Croat on Thursday, as he progressed to the quarter-finals 6-3 6-3 after an hour and 25 minutes at the ATP 500 clay court event.
In doing so, Nadal moved level with Arthur Ashe in 11th place on 683 victories in the Open Era, as he joined five other seeds in the next round.
Spain's Nicolas Almagro gained a measure of revenge on countryman Fernando Verdasco for his defeat in the US Men's Clay Court Championship final by progressing 6-3 6-3.
Verdasco saw off Almagro in Houston earlier this month, but was unable to produce a repeat performance as the world number 20 booked himself a final-eight clash with Nadal.
The pair are the only remaining Spaniards in the competition after fifth seed Tommy Robredo was beaten by the in-form Marin Cilic.
The Croat, who tasted title success in Zagreb and Delray Beach this year, won through 7-5 6-7 (3-7) 7-6 (7-5) against the world number 18, who had reached the quarter-finals or better on six occasions in Barcelona prior to this year.
Andrey Golubev was unable to add to his second-round scalp of Benoit Paire as he fell 6-0 6-4 to fourth seed Kei Nishikori, while Teymuraz Gabashvili built on the momentum of knocking out second seed David Ferrer.
The Russian moved into the quarter-finals with a 6-4 6-2 win over Spanish wildcard Inigo Cervantes and will meet ninth seed Ernests Gulbis in the next round.
The Latvian world number 23 won 10 of his 12 first service points during a dominant second set against Spain's Albert Montanes to win 7-5 6-1.
Germany's Philipp Kohlschreiber was too strong for Jurgen Melzer, progressing 7-5 6-3, while Santiago Giraldo edged past Austrian qualifier Dominic Thiem 4-6 6-4 7-5.