The 31-year-old player won the Australian Open earlier this year and.
Tsitsipas seemed exhausted after his semis victory over Nadal, a three-set match that the Greek won after two hours and 33 minutes of play on Saturday.
"I played the best match of the clay-court season for me", said Djokovic, "against arguably the best tennis player in the world on this surface". I had a tough match last night, so he took advantage of that. Tsitsipas contested his first ATP final in Barcelona in April and reached the Wimbledon Round of 16 in July, but he truly announced himself at the Rogers Cup in August. "Each week that I play in this tournament is a lot of memories, a lot of unforgettable memories", he said.
After starting slowly on clay last month after another knee injury, Nadal is hopeful of quick progress, but he has alluded to the fact that he could walk away if he cannot return to his best.
Tsitsipas displayed great character to keep things tight and make the top seed work, but Djokovic broke his resistance at 4-4 with a tremendous backhand down the line off the 20-year-old's smash from the baseline, followed by an errant forehand from the Greek.
Djokovic never let Tsitsipas get into gear in a final which lasted just over 90 minutes.More news: Trump bans use of telecom firms that pose national security risk
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"I was not playing my best after winning the Australia Open but I started this week well, not dropping a set all through".
In the women's final, Kiki Bertens beat two-time Madrid champion Simona Halep 6-4, 6-4. Tsitsipas hopes to win his third title of the year and the fourth title of his career.
While the eighth-time champion would love to extend the streak this week, Nadal said he was also "just playing for my happiness". "I've been really close, but I haven't been able to win".
"I needed to step up, Stefanos is very talented". He now has three Madrid Open trophies, adding to the ones he won in 2011 and 2016. He then served out to win the match.
The ninth-ranked Tsitsipas, the tour's form player in 2019 with 27 victories, lacked the intensity and aggressiveness that he showed against second-ranked Nadal and was overpowered by Djokovic. "I played some of my best tennis here". Djokovic has won five of his last seven final appearances overall and is 13-10 in final appearances on clay.