The win was the second straight Masters series title for the second ranked Serb, who defeated Roger Federer in the BNP Paribas Open two weeks ago in Indian Wells.
The world's top ranked players added another line to what has grown into one of tennis's great rivalries with the Spaniard holding a 22-18 edge.
But the Miami title continues to be one of the few to elude Nadal, who has now finished runner-up four times at Crandon Park, twice beaten in the final by Djokovic.
Both Nadal and Djokovic were well-rested after receiving walkovers into the final after opponents withdrew from the semi-finals, giving the tournament a mouth-watering championship matchup.
The contest featured everything one would expect from a matchup between the world's best with a title on the line, Nadal and Djokovic trading thundering groundstrokes right from the first point.
Both players had one break opportunity in an entertaining opening set and it was the Serb who made his count breaking Nadal to go up 4-2 and then holding serve for a 1-0 lead.
Djokovic quickly put his opponent under pressure, starting the second with a break and that was all he would need with Nadal unable to find a crack in the Serb's armor.
The match ended on another break and a dazzling rally, Djokovic sealing a clinical victory with textbook half-volley, then falling onto his back and punching his hands into the air in celebration.
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