After losing the first two sets, Tsitsipas recovered to take a 5-7 4-6 6-2 6-3 6-2 win and advance to the second round of the French Open.
It marked Musetti’s second brush with instigating a major disturbance at the French Open. In last year’s fourth round, he took a two-set lead against Novak Djokovic before being injured in the fifth.
The match started as it would eventually end – with Tsitsipas in complete control. He raced to a 4-1 lead in the first set and even had two breakpoints for 5-1, but Musetti held out, broke in exchange and tied the set to 4-4.
After trailing 4-5, Musetti embarked on a seven-game win streak to take the first set 7-5 and also take the second set.
On the other side of the field, Tsitsipas struggled to build momentum as he made 16 unforced forehand errors in the first two sets.
In the third set, however, the match turned on its head. Tsitsipas won 12 of the first 13 points and then rode to a 6-2 victory.
As Musetti tired and Tsitsipas rallied, the Greek made light work of the final two sets to round out the win.
“My attitude [changed]Tsitsipas told Eurosport after the game.
“I didn’t feel very good in the first two sets, there was something wrong with my game, but Lorenzo played really well, he didn’t give me a rhythm.
“Certainly, very happy that it ended like this. It was not easy for me in the first two sets, but positive, good effort at the end.”
Tsitsipas will face Czech qualifier Zdenek Kolar in the second round. His side of the draw is clear of Rafael Nadal, Novak Djokovic, Carlos Alcaraz and Alexander Zverev, giving him a clear run to the final for a chance to improve on his second place finish from last year.
Elsewhere in men’s singles, world No. 2 Daniil Medvedev advanced to the second round with a 6-2 6-2 6-2 win against Facundo Bagnis. However, fourteenth seed Denis Shapovalov crashed after a 6-3 6-1 7-6 (4) defeat to 19-year-old Holger Rune.