In the 40th meeting between the pair - a record for two opposing players in the open era - Djokovic produced a clinical performance as he defeated world No.1 Nadal 6-3, 6-3.
The Serb won three of his four break points, while Nadal failed to make the most of his only chance to break as Djokovic clinched victory in one hour and 24 minutes.
Djokovic, second in the ATP rankings, is now a four-time winner of the event, adding to his successes in 2007, 2011 and 2012, while Nadal has yet to lift the trophy after suffering another final disappointment.
The Spaniard was beaten by Roger Federer (2005), Nikolay Davydenko (2008) and Djokovic (2011) in his three previous final appearances in Miami.
Djokovic, who becomes the second player after Federer to win back-to-back titles at Indian Wells and Miami on two occasions, said at his trophy presentation: "I played a great match from the start to the end, everything was working really well. Bad luck Rafa, it's always a challenge and always a pleasure to play against you. Congratulations for a good week and good luck for the rest of the season."
He later added: "It feels great, I'm thrilled with my performance, it's been a fantastic day. I'm overwhelmed with the game I played. All in all it was an incredible tournament for me and the best performance at the right time."
Nadal said: "I want to congratulate Novak and his team, he did amazing with two great events in a row, winning in Indian Wells and now winning in Miami. That's very difficult to do, so just well done."