The pair are scheduled to meet in the semifinals after the tournament draw was made Friday, with defending champion Stan Wawrinka and three-time semifinalist Andy Murray also drawn to meet at that stage.
Djokovic -- who has lost three of the last four finals at Roland Garros -- begins his quest for a 12th major title against Taiwan's Lu Yen-Hsun.
Nadal, knocked out of last season's tournament by Djokovic in the last eight, starts his campaign against Australian Sam Groth and could meet home favorite Jo-Wilfried Tsonga in the quarters.
In the women's draw, defending champion Serena Williams -- targeting a fourth French Open title -- could meet 2010 winner Francesca Schiavone in round three.
Meanwhile, a viral infection has ruled Gael Monfils out of the tournament, which begins Sunday.
The Frenchman's agent said he had been "weakened and hospitalized in recent days."
Monfils missed the 2012 tournament after suffering a knee injury.
The three-time quarterfinalist reached the Monte Carlo Masters final earlier this year but was beaten in three sets by Nadal.
He becomes the second star to withdraw from the men's tournament after Roger Federer ruled himself out
with a back problem Thursday.
Federer's run of 65 straight majors came to an end when he announced on his Facebook page: "I regret to announce that I have made the decision not to play in this year's French Open.
"I have been making steady progress with my overall fitness, but I am still not 100% and feel I might be taking an unnecessary risk by playing in this event before I am really ready.
"This decision was not easy to make, but I took it to ensure I could play the remainder of the season and help to extend the rest of my career."