By Shrivathsa Sridhar and Amy TenneryNew York ― Novak Djokovic made his earliest exit at a Grand Slam in more than two decades as the Serb succumbed to injury and illness in a shock first-round defeat by unseeded Argentine Mariano Navone at the US Open on Sunday.The 39-year-old had arrived at Flushing Meadows with the aim of winning a fifth title and a record 25th Major crown overall but crashed out 7-6(5) 5-7 4-6 6-2 6-1 to send shockwaves through the final Grand Slam of the year.Former champion Daniil Medvedev and highest-ranked American Jessica Pegula advanced with little fuss earlier in the day, as players began their campaigns to grab a slice of the record prize purse of $108m up for grabs.The last time Djokovic lost in the first round of a Grand Slam was at the Australian Open in 2006 and the Serb did not go down without a fight despite battling shoulder and back problems and vomiting midway through the match.“I pretty much despised every moment I spent on the court for that,” Djokovic told reporters.With world No1 Jannik Sinner absent and defending champion Carlos Alcaraz returning after a lengthy spell out injured, Djokovic looked primed for a run at a record 25th Grand Slam.But Navone had not read the script and completed the biggest win of his career against his idol at Arthur Ashe Stadium.“I was 0-3 down, feeling a bit nervous out of respect for the star I was up against,” the world No 49 told ESPN.“It’s tough to play against Novak, he’s an idol. He never looked particularly comfortable with his shots or physically, that’s the truth.“In the fifth set he was a bit shaken. I had to focus on my game. You don’t get many chances to play an idol on a stage like this ... it’s incredible what I’m feeling; it’s all so exciting. It’s mad.”Russian Medvedev had crashed out in a chaotic first-round defeat a year ago but was all business on Sunday at Arthur Ashe Stadium, downing French qualifier Hugo Gaston 6-4 6-2 6-4 to quieten doubts after a frustrating run-up to the tournament.“The last couple of weeks were not easy,” said Medvedev, who exited the Cincinnati and Montreal tournaments early. “I’m happy that today I managed to produce high-level tennis.”Dozens of ticketholders were lined up long before the action kicked off and the home crowd was rewarded as world No 3 Pegula beat Romania’s Elena-Gabriela Ruse 6-3 6-2 in the first match at the showpiece stadium.The 2024 finalist next plays Sofia Kenin, who defeated fellow wild card Venus Williams 6-2 7-6(6) in a contest that began at 12.13am on Arthur Ashe Stadium in the latest starting women’s match in US Open history.Twice Grand Slam champion Barbora Krejcikova earlier became the first seeded player to exit the tournament, saving six match points before succumbing to Kamilla Rakhimova 7-6(4) 6-2 on the outer courts.Italian Jasmine Paolini survived a scare to beat Slovenia’s Veronika Erjavec 6-3 3-6 6-4 in the opener at Louis Armstrong Stadium to set up a meeting with compatriot Lucrezia Stefanini.Czech Jiri Lehecka kicked off the action on the Grandstand with a 6-1 7-6(5) 4-6 6-2 win over Spain’s Pablo Carreno Busta before Ukraine’s Marta Kostyuk swatted aside Australian Storm Hunter 6-4 6-1 at the same stadium.Kostyuk was joined in the next round by compatriot Elina Svitolina, who eased past Solana Sierra 6-1 6-2.Former champion Marin Cilic and 2022 runner-up Casper Ruud pulled out due to injuries shortly after the tournament got under way. Reuters