Novak Djokovic eyes Roger Federer record and French Open last 16 spot
Defending champion Djokovic, chasing a fourth title at Roland Garros and 25th career major, will go level with the retired Federer on 369 victories at the Slams if he sees off the Italian 30th seed and makes the last 16.
Djokovic has defeated Musetti four times in five meetings.
However, the Italian gave the Serb a major scare at the French Open in 2021 when he won the first two sets of their fourth-round clash before retiring injured in the decider.
"There is always that kind of conviction and belief inside of me I can win a Slam. That's the reason why I'm still competing at this level," said Djokovic.
Djokovic arrived in Paris under a cloud having not won a title or even reached a final in the season for the first time since 2018.
Adding injury to insult, he was accidentally hit on the head by a metal water bottle in Rome before suffering stomach problems in Geneva.
However, he hasn't dropped a set in two matches and cracked an impressive 43 winners past Spain's 63rd-ranked Roberto Carballes Baena on Thursday, dropping just seven games.
German fourth seed Alexander Zverev, who has made the semi-finals in each of the last three years, started this French Open by likely ending the Roland Garros career of 14-time champion Rafael Nadal.
"Since the draw came out, the only thing the tennis world was talking about was that match," said Zverev.
Best friends clash
"He won the tournament 14 times, so he deserves all the credit and respect and all the acknowledgements he gets. So after I beat him I felt that I had already won the tournament, but in the end it is only a first round."
On Saturday, Zverev tackles Dutch 26th seed Tallon Griekspoor and has shown no indication of being distracted by the start in Berlin of a trial against him over allegations of assaulting an ex-girlfriend.
Casper Ruud, the runner-up to Nadal and then Djokovic in the last two seasons, needed five sets to see off Spain's Alejandro Davidovich Fokina in the second round.
The seventh-seeded Norwegian faces Argentina's Tomas Martin Etcheverry who made the third round when his French opponent Arthur Rinderknech retired with a foot injury caused by kicking out in frustration at an advertising hoarding.
In the women's tournament, second seeded Australian Open champion Aryna Sabalenka and former world number two Paula Badosa must put their close friendship to one side when they clash for a last 16 place.
"It's always tough to play your best friend on tour, but we know how to manage that," said Sabalenka who has reached at least the third round in her past 14 Grand Slam appearances.
Mirra Andreeva, just 17, made the third round for a second successive year by seeing off former world number one and two-time major winner Victoria Azarenka in a three-set duel which ended in the early hours of Friday.
Andreeva, ranked 38, will face Peyton Stearns of the United States as she attempts to make the last 16 of a Slam for the third time.