Lorenzo Musetti picked up one of the biggest wins of his career Thursday, defeating No. 1 Novak Djokovic 4-6, 7-5, 6-4 at the Monte Carlo Masters for his first win over the Serbian player and second against a top-five player.

The tense contest had been suspended by rain for about an hour with the score tied 1-1 in the third set. When play resumed, Musetti broke for a 4-3 lead before serving out the victory on his fourth match point.

Playing only his second match on clay this season, Djokovic dropped his serve five times in the second set as both players struggled with accuracy in windy conditions. Djokovic led 4-2 but could not hold his lead with Musetti’s mix of drop shots and deep groundstrokes.

Djokovic was broken at love in the 11th game and was furious at the changeover, stomping on his racket and destroying it. Musetti kept his cool in the next game to serve out the set and force a decider.

“I’m struggling not to cry. It was a really long match, not easy conditions. It was a bit windy, cold,” Musetti said. “I’m really proud of myself. The rallies were long. It was a tough, physical battle. Beating Novak is something remarkable for me.”

Djokovic struggled with his movement Thursday, hitting 46 unforced errors and unable to find a solution to counter his Italian rival’s solid baseline shots. This was the third straight year that Djokovic has lost in the third round or earlier at this tournament.

“Well, (my) feeling is terrible after playing like this, honestly,” said Djokovic, who is expected to resume his preparations for the French Open next week at the Srpska Open in Bosnia-Herzegovina.

Their last meeting on clay was a grueling clash at the 2021 French Open, in which Djokovic battled back from two sets down to win when Musetti retired in the fifth set.

The 16th-seeded Musetti will next face seventh-seeded Jannik Sinner, who came from behind and saved a match point to get past No. 10-seeded Hubert Hurkacz 3-6, 7-6 (6), 6-1.

Sinner came out on top of a 22-shot rally when down 6-5 in the tiebreaker to remain in the match. Hurkacz lost the next two points, threw his racket in anger, then totally lost his focus in the decider.

“Playing against him, I knew already from the beginning that it was very tough to get into the rhythm,” Sinner said. “I think he served incredible in the first one and a half sets, and when I broke him the first time, the momentum changed a little bit.”

In another match, third-seeded Daniil Medvedev saved two match points in the deciding-set tiebreaker to rally past Alexander Zverev 3-6, 7-5, 7-6 (7).

Medvedev advanced to the quarterfinals in Monte Carlo for the second time and will next face Holger Rune. The sixth-seeded Rune advanced without playing when Matteo Berrettini withdrew due to an injury.

Jan-Lennard Struff reached the quarterfinals with a 6-1, 7-6 (6) win over fourth-seeded Casper Ruud as the German qualifier took another step in his comeback from an injury.

Previously ranked 29th, Struff dropped as low as No. 168 after suffering a foot fracture last year during a match in Miami, an injury that left him sidelined for more than two months.

Struff has enjoyed a good start to the season and returned to the top 100 last month but had not beaten anyone in the top 10 this year before taking on Ruud at the Country Club.

His aggressive style of play resulted in 37 winners and 23 points won at the net against Ruud, who dropped his serve four times.

Struff ended Ruud’s nine-match winning streak on clay. The 2022 French Open runner-up had won his past two tournaments on the surface, in Gstaad in July and in Estoril last week.

He will next face 2021 runner-up Andrey Rublev, who beat Karen Khachanov 7-6 (4), 6-2.

“We know each other too well. The first set was only mental. We didn’t show some tennis skills,” Rublev said. “But it was tough to show skills because the wind was really hard and the court was slippery and it was tough to do something.”

Also, two-time defending champion Stefanos Tsitsipas defeated Nicolas Jarry 6-3, 6-4 without dropping his serve.

“I had to deal with a few [tough] points, especially when he had break points,” said Tsitsipas, who next plays against eighth-seeded Taylor Fritz. “I dealt with those situations very maturely and played precisely, so it was great out there.”

Rafael Nadal and second-ranked Carlos Alcaraz pulled out of the tournament last week. Nadal has won the Monte Carlo title a record 11 times, including an Open era record streak of eight consecutive titles from 2005 to 2012. But the 22-time Grand Slam champion has been sidelined with a left hip flexor injury since the Australian Open.

The Associated Press and Reuters contributed to this report.