Djokovic dominated a clearly exhausted Tsitsipas less than 24 hours after the 20-year-old Greek had stunned five-time champion Nadal in a semifinal which ended around midnight on Saturday.
Nadal seemed to have the momentum after winning 13 out of 16 points at the end of the second set but he spurned two break points in the decider before Tsitsipas broke twice for 5-2.
"It wasn't my best night", Nadal said after his third failure for a clay court title.
Tsitsipas will be playing in his fourth final of the season and will have a chance to become the first player to win three titles this year, adding to his triumphs in Estoril and Marseille.
"He played quite smart, tried moving me around the court".
There are just two weeks to go to the year's second tennis Grand Slam - the French Open in Paris.More news: French troops rescue four hostages in Burkina Faso raid
"Obviously I needed to step in", Djokovic said. "I played some good tennis and will be No 4 in the world on Monday, it is just all wonderful things", Bertens said.
On the women's side, top-ranked Naomi Osaka reached the quarterfinals with a straight-set win over Aliaksandra Sasnovich and will next face Belinda Bencic, who dropped only two games in her victory over Kateryna Kozlova. But he's had a terrific week and it's a big win obviously for me today and in this tournament.
"This is a sport and, in a sport, it's a matter of winning and sometimes, losing and accepting both as naturally as possible". I felt I was dictating the play and played my best tennis so far this week. He was beaten by Nadal in the Australian Open semifinals for his best-ever showing in a Grand Slam.
"It is really tough to physically cope with that and I think that's the biggest challenge if you're going to play all of those guys in the same tournament". He had a very late night, I could see he wasn't as dynamic in the movements as he was last night and that's probably due to the long match, but he's had a terrific week. On the rare occasions the Spanish clay-court king was dethroned, it generally took one of the world's best players, either Federer or Djokovic, to make it happen.
Djokovic, victor in Madrid in 2011 and 2016, was fully rested after his quarter-final opponent Marin Cilic had withdrawn because of food poisoning, while Thiem had to dig deep to beat Roger Federer in a gruelling three-setter.
Later, Rafael Nadal bantered Tsitsipas."I wouldn't want to play with Tsitsipas as a junior without an umpire because he doesn't know the difference between a ball in and a ball out".