The third-seeded Swiss will open his quest for a second Musketeers Cup against Italian Lorenzo Sonego, the world number 73, but faces a potentially tricky quarter-final against young Greek Stefanos Tsitsipas who beat him at this year’s Australian Open.
Defending champion Nadal, seeded second, will open up against a qualifier as he aims for a record-extending 12th title at Roland Garros and could face Japanese Kei Nishikori in the last eight.
World number one Novak Djokovic, who is looking to hold all four majors for the second time in his career, will take on Hubert Hurkacz with a possible quarter-final against German Alexander Zverev.
Fourth seed Dominic Thiem, the 2018 runner-up to Nadal, could face Argentine eighth seed Juan Martin del Potro in the quarters.
The Australian men all have chances to advance before facing even tougher opponents. Nick Kyrgios faces Brit and world number 44 Cameron Norrie while Alex de Minaur seeding at 21 hands him a match with American Bradley Kahn. Wildcard Alexei Popyrin plays French youngster Ugo Humbert.
The women
In the wide-open women’s draw, world number one Naomi Osaka will kick off her bid for a maiden French Open title against Slovak Anna Karolina Schmiedlova.
Defending champion Simona Halep of Romania, the third seed, will take on Australian Ajla Tomljanovic after being drawn in the same half as Osaka.
Serena Williams will face Vitalia Diatchenko in only her second match on clay this season after she retired from the Italian Open ahead of a second-round match against her sister Venus due to a knee injury.
With 23 singles Grand Slam titles to her name, the 10th-seeded American, on a quarter-final collision course with Osaka, is one short of the all-time record of Margaret Court.
One of the first-round clashes to watch is 2017 champion Jelena Ostapenko against two-times Grand Slam winner Victoria Azarenka, with the winner likely to take on Osaka in the second round.
Second seed Karolina Pliskova, the champion in Rome last weekend, starts against Madison Brengle of the United States.
If the seedings prove an accurate indicator, Osaka would face Australia's Ashleigh Barty in the quarter-finals, Halep would meet two-time Wimbledon champion Petra Kvitova, 2018 runner-up Sloane Stephens would tackle Madrid champion Kiki Bertens while Angelique Kerber of Germany would be Pliskova's last-eight rival.
Kerber is attempting to complete the career Grand Slam with a French Open title.
