Djokovic aggressively put away the Spaniard - who is now 0-4 in his attempts to win at Key Biscayne - in just an hour and 23 minutes, waging a consistent and unrelenting attack on the world's No. 1 player.
Nadal said that his serve was going to be key and that he would have to play above his normal level to be able to beat Djokovic, ranked No. 2, but he was unable to muster the required go-power to emerge victorious.
Despite the result, Nadal will remain ranked No. 1 and Djokovic No. 2.
Nadal began the hard-court match with great intensity - even though he prefers to play on clay - but the Serb was able to do him damage on practically every one of the volleys, sending his countershots deep, wide just inside the lines or rushing the net when the Spaniard gave him the chance.
In the sixth set, Djokovic easily broke his rival's service, even though the Spaniard enjoyed the support of the mainly Latino local crowd.
This was the pair's 40th encounter, with Nadal emerging triumphant on 22 of the matchups, although Djokovic had won 13 of their 20 past confrontations on fast courts like Miami.
After winning the first set 6-3, Djokovic went on to break Nadal's service again in the second set.
Djokovic had won in Miami on three previous occasions - 2007, 2011 and 2012 - and has exceeded Pete Sampras in the number of titles at Key Biscayne, and throughout his contest with Nadal appeared to have the Spaniard corralled and unable to mount an effective counterattack.
Given Sunday's result, Spanish men fell to 0-7 in Key Biscayne finals.
The Sony Open is one of the biggest hard-court events on the ATP and WTA calendars.