Djokovic, who won the tournament in 2009 and 2010, defeated Carlos Berlocq 6-1, 6-3. He set the tone for the match by taking the first game in less than 2 minutes. Djokovic won 56 percent of the points off Berlocq's serve and 59 percent overall.
He did lose his serve twice in the second set but countered that with four breaks in Berlocq's five games serving.
Third-seeded Jo-Wilfried Tsonga also moved into the third round. Nikolay Davydenko said he couldn't play due to a toe injury, giving Tsonga the walkover win.
Jurgen Melzer knocked out sixth-seeded Alexandr Dolgopolov 7-6 (11-9), 2-6, 6-1 by losing just 10 points -- two on serve -- in the third set. That earned Melzer a quarterfinal spot opposite Djokovic.
Also Wednesday, Florian Mayer rallied for a 3-6, 6-3, 6-2 win over Marius Copil.
Swim Week Miami Beach 2014 [PHOTOS]