The 22-time major champion was pitted against Hungarian Marton Fucsovics first up, while 24-time Grand Slam winner Djokovic drew Australia’s Matt Ebden. Djokovic holds a 30-29 edge over Nadal in their head-to-head record.
Home hope and 14th seed Arthur Fils looms as a possible third round opponent for the winner before eighth-seeded Greek Stefanos Tsitsipas and the reigning Olympic champion, third-seeded German Alexander Zverev, as potential hurdles to the final.
Zverev, who opens against Spain’s Jaume Munar, could run into American seventh seed Taylor Fritz in his quarterfinal.
This year’s Wimbledon and Roland Garros champion, Carlos Alcaraz, opens against Lebanon’s Hady Habib, a player he has never met.
The second seed could meet 15th seed Alejandro Tabilo, of Chile, Australian fifth seed Alex de Minaur – who returns following a Wimbledon-ending hip injury – and fourth seed Daniil Medvedev in succession to reach the final.
Medvedev, who starts against Australian Rinky Hijikata, could meet Norwegian sixth seed Casper Ruud – a two-time Roland Garros finalist – in the quarterfinals should both advance.