World number one Sinner is the overwhelming favourite in the men's draw in the absence of injured rival Carlos Alcaraz.
He will be hoping for a comfortable victory in his first-round tie against French wildcard Clement Tabur in the night session on Court Philippe Chatrier, after a gruelling, albeit successful, clay-court season.
The Italian clinched his sixth successive Masters title at the Italian Open earlier this month, completing the set of all nine 1000-level trophies, adding to tournament wins on clay in Monte Carlo and Madrid.
Sinner will be playing at Roland Garros for the first time since his agonising loss to Alcaraz in last year's final, in which he led by two sets and missed three championship points.
He is on a 29-match winning streak and has not lost since a defeat by Jakub Mensik in Doha in February.
"Everyone is trying to beat (me), but that's also the most normal thing," said Sinner.
"You need to be ready. Best-of-five matches, they are a bit different.
"It gives you a little bit more time to understand how to beat a player, and even if you have a wrong start, then potentially you can find a way in."
Tabur will be playing in the main draw of a Grand Slam for only the second time at the age of 26, after a first-round loss to Corentin Moutet as a qualifier last year.
The world number 171 has lost all of the other six qualifying matches he has played at the majors.
Follow the men's side at Roland Garros here.
Gauff and Sabalenka headline women's side
Gauff begins her defence of the Coupe Suzanne Lenglen against fellow American Taylor Townsend.
The women's fourth seed has struggled for consistency since beating Aryna Sabalenka in last year's title decider in Paris, but did reach the Italian Open final before losing to Elina Svitolina.
Gauff could reach at least the quarter-finals for a sixth successive year at Roland Garros, where she has by far her best record in Grand Slam events.
"Whenever I come to this tournament, I don't even think about my past results here," she said.
"It's obviously different thinking about last year, but I don't know, last year feels like 10 years ago."
Townsend won her only previous meeting with Gauff at an ITF event in Charleston seven years ago, when her opponent was a 15-year-old qualifier.
Sabalenka appeared poised to be a strong favourite for the French Open when she completed the 'Sunshine double' by emerging victorious at both Indian Wells and in Miami in March.
But the world number one enters Roland Garros with question marks around her form after a Madrid Open quarter-final loss to Hailey Baptiste and another shock defeat in the third round against Sorana Cirstea in Rome.
She believes she will be fresh, though, when she starts her latest tilt at a maiden French Open title, facing Jessica Bouzas Maneiro of Spain.
"I struggled at the beginning of the clay court (season) physically, to be honest, but right now I feel 100 per cent," Sabalenka said.
"We did a great recovery. We focused on recovery and making sure that I'm healed everywhere and I'm ready to go."
Four-time Grand Slam champion Naomi Osaka, a potential last-16 opponent for Sabalenka, plays Laura Siegemund of Germany, while the Philippines' Alexandra Eala faces a tough test against 17th-seeded teenager Iva Jovic.
