It was the 24-year-old Serb's third Grand Slam title, to add to his 2008 and 2011 Australian Open victories, and 50th win his last 51 matches.
Djokovic, who will succeed Nadal as world number one on Monday, Jul 4 also denied the Spaniard, the champion here in 2008 and 2010, an 11th Grand Slam title.
Djokovic went into the final with a 11-16 losing record against Nadal over their five-year rivalry but having won all four of their clashes in 2011 and all in finals.
Serve dominated until the 10th game when from 30-0 up Nadal handed his opponent a set point with a forehand error which Djokovic gobbled up, forcing another wild forehand out of the Spaniard to take the opener after 41 minutes.
The Serb had been the more convincing in the rallies and Nadal, who committed just seven unforced errors in his semi-final win over Andy Murray, was already up to eight by the time Djokovic was 1-0 ahead in the second set.
Djokovic was taking control of the final and was a break up at 2-0 when he brilliantly anticipated a Nadal drop shot before scampering across court to execute a wonderful, wrong-footing backhand.
The Serb broke again for a 5-1 lead when a powerful drive left Nadal scrambling, and off balance, and he could only pat the return wide. A confident hold to love gave Djokovic the set 6-1 when Nadal found the net.