Last season's finalists look set to go head-to-head early in the competition and continue their long-standing rivalry. Eugenie Bouchard suffered a surprise first round defeat.
Rafael Nadal and Novak Djokovic are on course for a quarterfinal showdown at the French Open after the pair comfortably progressed on the first day's play at Roland Garros.
The Spaniard has lost only once at the French Open and is keen to end a troubled period with his 10th title in Paris. Sixth-seed Nadal had little problems in dispatching 18-year-old Frenchman Quentin Halys 6-3, 6-3, 6-4 and now prepares to face countryman Nicolas Almagro.
Meanwhile, the number-one ranked Serb has one gap on his CV: winning the French Open. He showed early focus in his match with Jarkko Nieminen who went down 6-2, 7-5, 6-2.
"It was a test; it was a challenge for me to come back to the court again after first match after Rome finals. I was aware of the quality and experience of my opponent today, who has shown, and especially in the second set, why he's been around the tour and a successful, consistent player for so many years," the 28-year-old said.
Djokovic, the current Australian Open and Wimbledon champion, hasn't lost in his last 23 matches. The impressive Serb went head-to-head at the 2014 French Open with Nadal who secured his fifth consecutive championship at Roland Garros.
Wednesday's French Open card sees Roger Federer take on Spaniard Marcel Granollers and fifth-seed Kei Nishikori face Thomaz Bellucci from Italy.
Meanwhile, Eugenie Bouchard's miserable 2015 continued as she became the highest-seeded player to go out of the French Open so far.
The 21-year-old reached three consecutive Grand Slam semifinals last year and won a place in the Wimbledon final. But since a change of coach, Bouchard has had a dip in form despite reaching the quarterfinals of the Australian Open.
Bouchard lost 6-4, 6-4 to 44th-ranked Kristina Mladenovic of France who handed the youngster her eighth defeat in the last nine matches.
"Everyone has highs and lows in their career. This is a little bit of a low point for me," said the sixth-seed Canadian. Honestly, I don't know what to say. It's been kind of the same as how I have been feeling recently on the court. Just not like myself."
Women's number one Serena Williams took just 59 minutes to defeat Andrea Hlavackova (6-2, 6-3) and faces Germany's Anna-Lena Friedsam in the second round.