Absence of Roger Federer from the draw for the first time since 1998 will be felt the most.
Djokovic is bidding for a seventh title at the All England Club to move level with US great Pete Sampras.
The seedings for Wimbledon were announced on Tuesday, with Djokovic and Nadal being Nos. 1 and 2, respectively, in the men's draw because of the absence of Daniil Medvedev and Alexander Zverev.
Medvedev returned to No. 1 in the rankings this week, with Novak Djokovic dropping to No. 3, and acknowledged that may add to his opponents' motivation in Halle.
While the Serb will ruin the fact that he wasn't able to produce in the moments that really mattered, Nadal will not care one iota about how this win was got.
The German third seed claimed a 6-4, 6-4, 4-6, 7-6 (9/7) victory over 19-year-old Spanish sensation Alcaraz after three hours and 18 minutes.
The match ended in cool conditions under the Court Philippe Chatrier lights, with many fans covering themselves in blankets as the match stretched from May into June.
Nadal turns 36 on Friday when he will face third-seeded Alexander Zverev in the semifinals.
Nadal, who turns 36 on Friday, puts his record of 109 wins and just three losses in Paris since his title-winning debut in 2005 on the line against the defending champion.
"I'm ready for it," Djokovic said. "I hope to be able to give myself a chance to play at the highest level possible," Nadal said, "and then let's see.
Nadal got through a five-set win over Felix Auger-Aliassime in the fourth round on Sunday to set up a record 59th matchup against Djokovic. He has an overall win-loss record of 109-3 at Roland Garros.
As the sun and temperature descended and the chants of “Ra-fa! Ra-fa!” filled the evening air, the man known as the King of Clay showed precisely what this meant to him.
Novak Djokovic said it breaks my heart to see former coach Boris Becker in prison over charges relating to a 2017 bankruptcy.
Novak Djokovic intends to defend his title at Wimbledon and supports the decision by the ATP men’s tour to withhold ranking points from that tournament.
World number one Djokovic, bidding for a third Paris title to move level with Nadal on 21 Grand Slams, comes into the tournament with a sixth Italian Open under his belt.