However, Nadal conceded that the match will be tough and he has to be at his very best against the world number two.
More Almagro errors flowed to give Djokovic another break for 6-5 and he served out for the match.
Djokovic has won 26 of their previous meetings including the last seven. In his 13-match winning streak, he did not encounter a top-five player and Djokovic will be looking to end his streak.
Nadal is now the strongest tennis player in the world, despite the fact that the Spaniard takes only the fifth place in the ATP rating.
The defending champion had fewer problems against the 35-year-old Spaniard than in his three-set second-round test with Nicolas Almagro a day earlier.
Coric will try to win his second tournament this season.
However, since last summer, and joining forces with a new coach in Dani Vallverdu, everything had changed: Something seemed to click, the confidence returned, along with the wins.
Play starts for the Madrid Masters quarter-finals at 12pm (11am BST).
Off the back of triumphs in Monte Carlo and Barcelona, the clay-court specialist's French Open preparations are gathering pace, with Goffin defeated 7-6 (7-3) 6-2 on Friday.
Djokovic still flashes the defensive ingenuity, tireless consistency, and precision shot-making on the run that has won him 12 majors-everything's clearly still there. "I know that I have to play at my highest level, perhaps similar to today or even better". He schooled a clearly frustrated Tomas Berdych who just could not get it together when it counted, except when it came to killing his racquet at the end.
The exciting Australian was riding a fine wave of form, having twice beaten Novak Djokovic this year and coming within points of denying Roger Federer in the semis of Miami, where he finally lost the third of three tiebreaks.
It was Djokovic's first match since splitting with longtime coach Marian Vajda. Fognini served for the set at 5-4 but was not able to capitalize on his chance. Bet: the victory of Rafael Nadal.
"I played a lot better", said Nadal, who struggled in a three-set win over Fabio Fognini on Wednesday. When you win every single match in every tournament, that is abnormal. He lost to Albert Ramos-Vinolas in the third round in Monte Carlo after blowing a 4-0 lead in the deciding set, then was eliminated by Thiem in the semifinals of the Barcelona Open.
The reigning French Open champion won their first meeting easily in the second round of the French Open in 2010, and the sixth seed won their second encounter in the semifinals in Basel in 2011, 2-6, 7-6 (4), 6-0. He went on to reach four Masters quarter-finals, and was now aiming for his first in Madrid.
"I'm going to think about who I want in my team", the Serb said Wednesday. "Right now I don't have anyone yet, but I think by the French Open or after the French Open I (am) already going to have someone".
Kerber will take over the top ranking on Monday as a result of earlier Madrid results. Djokovic won 6-1, 4-6 and 7-5.
Lopez, ranked 38 in the world, beat Gilles Simon of France 6-3, 3-6, 7-6.