Djokovic were placed on a mouth-watering French Open quarter-final collision course in Friday's draw.
Nadal is seeded a lowly sixth this year after slipping to seven in the rankings and as a result was always likely to face one of his major rivals in the last eight.
"It's very strange," admitted Nadal, promoted to the sixth seeding after the injury-enforced pull-out of Canada's Milos Raonic. "It's never happened before.
"But I have to play four matches to get to the quarter-finals. I have to be ready for the first round."
Nadal defeated Djokovic in the 2012 and 2014 finals, but the top-seeded Serb, who turned 28 on Friday, is the overwhelming favourite for a maiden Roland Garros title this year.
Djokovic goes into the French Open, which starts Sunday, riding a 22-match unbeaten streak and has already captured a fifth Australian Open and Masters crowns in Indian Wells, Miami, Monte Carlo and Rome this year.
Djokovic, bidding to become only the eighth man to complete the career Grand Slam, starts his campaign in Paris against experienced 33-year-old Finn Jarkko Nieminen while Nadal begins against 18-year-old French wildcard Quentin Halys, the world number 304.
The world number one said he wasn't surprised by the draw which put Nadal into his section.
"I think that even a few weeks ago when Rafa dropped from the top four, I think people already started talking the eventual quarter-finals with one of the top guys. So it's not a surprise," said the Serb.
"It's been something that was building up already for a few weeks. But again, it's a draw. You can't affect it. There is always a chance that that's gonna happen."
The other potential quarter-finals could see second seed Roger Federer, the 2009 champion, face Swiss compatriot Stan Wawrinka.
Third seeded Andy Murray was drawn for a potential last-eight clash against David Ferrer while Tomas Berdych could tackle Japan's Kei Nishikori.
Federer, the 2009 champion, starts against a qualifier but has Latvian 24th seed Ernests Gulbis, who knocked him out in the fourth round last year, also in his section.
French star Gael Monfils, who defeated Federer at the Davis Cup final in 2014, is a potential fourth round opponent.
Murray is a possible semi-final opponent for Djokovic as well as Nadal with the Scot, the champion on clay in Munich and Madrid this year and with a 10-0 record on the surface, starting against a qualifier.
Murray, a semi-finalist last year, could face Australian hope Nick Kyrgios, who beat Federer in Madrid, in the third round.
In the women's singles, top seed Serena Williams was handed a tough draw which could see the American taking on old rival Victoria Azarenka and sister Venus before the quarter-finals.
Williams, the 2002 and 2013 champion and just three majors shy of matching Steffi Graf's Open-era record of 22 Grand Slam titles, starts against a qualifier but could meet sister Venus in the last 16.
Two-time Australian Open winner and former number one Azarenka is a potential third round opponent for Williams.
Adding extra spice to the draw is the presence of bitter American rival Sloane Stephens in Serena's half.
Stephens could face the two-time champion in the last 16 but she starts against Venus.
n contrast, second seeded defending champion Maria Sharapova starts against experienced Estonian Kaia Kanepi and could tackle Spanish claycourter Carla Sanchez Navarro in the quarter-finals.
Former number one Caroline Wozniacki is a possible last-eight opponent for Williams.
Third seed Simona Halep, the runner-up in 2014, could meet 2008 champion Ana Ivanovic in the quarter-finals.
Petra Kvitova, the fourth-seeded Wimbledon champion is in Serena's half of the draw and a potential semi-final rival.
Kvitova knocked the American out of Madrid this month, ending the 19-time major winner's 27-match win streak.