The Spaniard, playing his 1,000th ATP match, suffered just the 14th 0-6 set of his career, claiming just 33 percent of first serve points won and making a string of unforced errors.
After looking badly out of sorts, Nadal was able to rediscover his form in the second set and in the end ran out a comfortable winner.
Nadal will next face France's Nicolas Mahut, who beat Argentine Guido Pella 6-4 6-3.
Japan's Kei Nishikori came through a tough test against Spaniard Fernando Verdasco 7-6 (7/2), 6-7(5/7) 6-1.
Last year's beaten finalist, Nishikori will face Argentine Federico Del Bonis, who beat Germany's Jan-Lennard Struff 7-6 (7/5), 6-1.
Verdasco has yet to post a win against a top ten opponent this year but showed plenty of spirit in a two hours 44 minute contest on center court at Crandon Park fighting back to win a second set tie-break.
But Nishikori stepped up in the third, running away with the set to ensure his progress.
"I knew it was going to be a tough one," Nishikori said. "Fernando is a very solid player. He has a great serve and great groundstrokes. I knew it was going to be long rallies.
"But it was a shame when I was up a break in both first and second sets and both went to 7-6. I made some mistakes when I was up a break. But in the third set I was very focused," he added.
Injury-plagued world number five Milos Raonic pulled out of the tournament shortly before his match against American Jared Donaldson, citing a recurrence of a hamstring injury.
Canada's Raonic originally suffered the injury in the semi-final at Delray Beach and was forced to forfeit the final against American Jack Sock. He then missed this month's Masters event at Indian Wells.
source: news.abs-cbn.com
