Djokovic was clearly tense during a four-sets win over the Italian and had angrily lambasted his box after failing to convert a match point before damaging the side of the court.
After sealing the 6-2 6-3 6-7 (5-7) 7-5 win just moments later, Djokovic exploded again, roaring up at his box with his veins bulging.
It was a curious match between the world No. 1 and the ninth seed.
Djokovic appeared in total control when two sets to love up but his Italian opponent refused to lie down.
After hanging on to force a breaker, Berrettini capitalised after some tight shots from Djokovic to take the match into a fourth set.
Andy Murray, the former world No. 1 from Great Britain, was in no doubt about the result at that stage, tweeting: ‘I’d put my house on Djokovic winning this match.’
He was proved right but it was far from straightforward.
The crowd were becoming more vociferous in their support for Berrettini and then there was a lengthy delay to the match as the supporters were ejected from the stadium due to the 11pm Covid curfew in Paris.
Djokovic lost control when he failed to convert a match point, swiping his racquet towards his box while screaming before kicking an advertising board at the side of the court.
Once the match was sealed he let out a huge emotional release, roaring to the heavens.
On his outburst, former world No. 1 Mats Wilander told Eurosport: ‘The emotion at the end, that’s what he is holding in the whole time.
‘That’s why I am so impressed and proud to be part of the sport of professional tennis because these players have gone through very, very difficult times and they are holding a lot of emotion in.
‘You see there with Novak that it is emotional for these guys. It is a tough job during the pandemic to be a traveling tennis player.’
He will now go on to face Nadal for a 58th time and ninth time in Paris.
Nadal is chasing a 14th French Open title and 21st major win in total, Djokovic will win a 19th major if he goes on to win a second French Open.
The winner of Djokovic-Nadal will go on to face either Greece’s Stefanos Tsitsipas or Germany’s Alexander Zverev.
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