Nishikori battled to beat Italian Alessandro Giannessi in five sets in the opening round and was involved in another match that went the distance in Paris.

Khachanov led by two sets to one, but Nishikori showed great resilience to complete a 4-6, 6-2, 2-6, 6-4, 6-4 victory in four hours on Court Philippe-Chatrier.

Nishikori, a three-time Roland Garros quarter finalist, has now won 10 of his past 11 five-set matches.

Switzerland’s Henri Laaksonen will be Nishikori’s next opponent after he produced one of the biggest upsets of the day.

The world number 150 saw off Spanish 11th seed Roberto Bautista-Agut 6-3, 2-6, 6-3, 6-2 in two hours and 21 minutes.

The highest men's seed in action today was Russia's Daniil Medvedev, the second seed, who recovered from a set down to defeat American Tommy Paul.

Playing in the night session behind closed doors on Court Philippe Chatrier, Medvedev lost the first set 6-3 before bouncing back to win the next three 6-1, 6-4, 6-3.

Sixth seed Alexander Zverev of Germany did not have it all his own way against Russian qualifier Roman Safiullin but came through with a 7-6 (7-4), 6-3, 7-6 (7-1) win to seal his place in the third round.

"The match definitely wasn't easy," said Zverev who won from two-sets-to-love down against German qualifier Oscar Otte in the opening round.

"I'm happy not to have played another five-setter.

"I think it's going to be important for me during the course of this tournament."

Zverev will now face Serbian Laslo Djere, who overcame compatriot Miomir Kecmanovic 4-6, 4-6, 6-3, 6-2, 6-3.

Norwegian Casper Ruud reached the third round of the French Open for the third successive year with a 6-3, 6-2, 6-4 victory over Poland’s Kamil Majchrzak.

There was also another straight sets win for Greek fifth seed Stefanos Tsitsipas who saw off Spain’s Pedro Martinez 6-3, 6-4, 6-3.

Tsitsipas, who is hotly tipped to reach his first French Open final, can now look forward to tackling American giant John Isner who battled past Serbia's Filip Krajinovic with a 7-6 (8-6), 6-1, 7-6 (7-5) triumph.

There were also victories for Spain’s Alejandro Davidovich Fokina, Italian Fabio Fognini, Argentina’s Federico Delbonis and American duo Marcos Giron and Reilly Opelka.

In the women’s draw, three-time French Open champion Williams of the United States dropped a set before finding an extra gear to defeat Romanian Mihaela Buzarnescu 6-3, 5-7, 6-1.

Russian Daria Kasatkina produced a superb display to stun 10th seed Belinda Bencic of Switzerland 6-2, 6-2.

Bencic's loss means there are no top 20 players remaining in the bottom quarter of the draw, with Japan’s Naomi Osaka, Canada’s Bianca Andreescu and Kiki Bertens of The Netherlands all exiting the tournament.

The only player left in that quarter who has previously reached a Grand Slam semi-final is 20th seed Marketa Vondrousova.

The Czech needed just 62 minutes to dismiss French wildcard Harmony Tan 6-1, 6-3.

Vondrousova’s compatriot Katerina Siniakova emerged the victor in a match that lasted almost three hours against Veronika Kudermetova, winning 7-6 (9-7), 5-7, 7-5.

In the battle of the Belarusians third seed Aryna Sabalenka won 7-5, 6-3 against compatriot Aliaksandra Sasnovich.

World number 85 Tamara Zidansek of Slovenia backed up her first-round upset of Andreescu with a comfortable 6-4, 6-1 defeat of American Madison Brengle.

There was double delight for Slovenia as Polona Hercog downed home favourite Caroline Garcia 7-5, 6-4.

Romania’s Sorana Cirstea was forced to dig deep to beat Italian Martina Trevisan – a surprise quarter-finalist last year - 6-4, 3-6, 6-4 in two hours and 37 minutes.

Two-time Grand Slam winner and former world number one Victoria Azarenka extended her run at Roland Garros with a 7-5, 6-4 success against Denmark’s Clara Tauson.

The Belarusian moves through to the third round where she will meet American Madison Keys who defeated Canadian Leylah Fernandez 6-1, 7-5.

Spain’s Paula Badosa and American Danielle Collins lost just two games in their impressive victories over Montenegro’s Danka Kovinić and Ukraine’s Anhelina Kalinina respectively.

Russian Anastasia Pavlyuchenkova also looked in fine form as she thumped Australia’s Ajla Tomljanović 6-2, 6-3.