Nadal improved his record at Roland Garros to 66-1, and stretched his winning streak at the clay-court major to 35 straight.
But it didn't look too good at the start for the top-seeded Spaniard. Djokovic won the first set and looked to be in control of nearly every point. The combination of Nadal finding his range and the heat on court, however, started to take its toll on the second-seeded Serb.
Both players used ice-filled towels to cool themselves during changeovers, but Djokovic also looked like he vomited a bit as he was heading for the first changeover in the fourth set.
Djokovic also appeared out of sorts in the third set. Trailing 3-0, he wobbled as he went to take his seat on the bench for the changeover. And in the final set, with Nadal leading 5-4, Djokovic poured cold water on his head and on each forearm in an effort to cool off.
Nadal was broken once in the first set, and once again in the second. He was able to recover the second break, however, as he started to find his range on Court Philippe Chatrier, the stadium Nadal calls his favorite place in the world to play.
He ended up breaking Djokovic to win the second set, and then again to win the third and yet again to win the fourth.
On match point, Djokovic double-faulted for the third time. Nadal dropped to his knees before shaking hands with Djokovic and then climbing into the crowd to celebrate with his team.
Nadal, who will retain his place at the top of the rankings with the victory, has now won 14 Grand Slam titles, tied for second among the men with Pete Sampras. Only Roger Federer, with 17 majors, has more.
But Nadal is the only player to have won the same Grand Slam tournament nine times, and is the first to win five straight French Open titles. He also won at Roland Garros from 2005-08, but lost for the only time in the fourth round of the 2009 tournament. Federer went on to win that year, completing a career Grand Slam.
Nadal is 23-19 against Djokovic overall, and 6-0 against him at Roland Garros. Djokovic took Nadal to five sets in last year's French Open semifinals, and lost in four in the 2012 final.
Entering Sunday's match, however, Djokovic had won their previous four meetings, including winning the title in Rome on clay.
The six-time major champion still needs a victory at the French Open to complete a career Grand Slam.