NEW YORK - Japanese fourth seed Kei Nishikori, last year’s runner-up, crashed out in the opening round of the US Open on Monday while Serena Williams lost another high-ranked rival as Serbian seventh seed Ana Ivanovic was also sent packing.

The year’s final Grand Slam tournament began with drama on the Flushing Meadows hardcourts as 41st-ranked Frenchman Benoit Paire ripped Nishikori 6-4, 3-6, 4-6, 7-6 (8/6), 6-4 and Slovakia’s 50th-ranked Dominika Cibulkova ousted seventh-seeded Ivanovic 6-3, 3-6, 6-3. “To beat Nishikori, for me, it was impossible to imagine this,” Paire said. “I’m really happy.”

Paire, who saved two match points, fired 21 aces to only three for Nishikori and blasted 64 winners, 30 more than Nishikori, with 67 unforced errors, 31 more than the Asian number one. Nishikori enjoyed his highest seed for any Grand Slam event all-too briefly, walking off Louis Armstrong Stadium with his head down after his third first-round exit in New York in five years.

After dropping the first set, Nishikori rallied and appeared poised to advance after seizing command of the fourth-set tie-breaker, a backhand winner giving him a 6-4 advantage and two match points. But Nishikori smacked a forehand long on his first and Paire, who won his first ATP title last month at Bastad, smashed two service winners to reach set point. Nishikori netted a forehand and the match went to a fifth set. Paire broke Nishikori in the fifth game and held to the finish, dispatching him after three hours and 14 minutes. “I had a really good serve today,” Paire said. “I saved two match points so I’m really lucky.”

Nishikori had won three titles this year included a US Open warm-up win at Washington that saw him avenge last year’s US Open final loss to Croatian Marin Cilic. Serb star Ivanovic made her first opening-round exit at the US Open since 2009. “It’s definitely very disappointing with the loss because I felt like I had great preparation,” Ivanovic said. “I felt like I’ve been improving. That’s why it’s so disappointing. I just have to keep working.”

Ivanovic, the 2008 French Open champion who was a semi-finalist this year at Roland Garros, had been the highest-ranked rival in Williams’s half of the draw following the injury-enforced withdrawal of Maria Sharapova. That status now falls to Czech eighth seed Karolina Pliskova with Spanish 10th seed Carla Suarez Navarro the highest-rated possible semi-final opponent for three-time defending champion Williams, who is trying to complete the first calendar Grand Slam since Steffi Graf in 1988 and win her 22nd major title to match Graf’s Open Era record.

Poland’s 15th-seeded Agnieszka Radwanska remained Williams’s highest-ranked potential foe in the round of 16 by beating Czech teen Katerina Siniakova 6-2, 6-3. Williams will open in the first Ashe night match against Russia’s 86th-ranked Vitalia Diatchenko. World number one Novak Djokovic meets Brazil’s Joao Souza while Spanish eighth seed Rafael Nadal, a possible quarter-final foe for Djokovic, faces Croatia’s Borna Coric, who won their first meeting last year at Basel.

Sharapova withdraws with leg injury: Russian third seed Maria Sharapova withdrew from the US Open on Sunday with a right leg injury, easing the path to a calendar-year Grand Slam for top-ranked Serena Williams.

US Open tournament director David Brewer announced Sharapova’s exit, which allowed qualifying lucky loser Daria Kasatkina of Russia into the draw in Sharapova’s place. “Unfortunately I will not be able to compete in this years US Open,” Sharapova said in a Twitter posting. “I have done everything possible to be ready but it was just not enough time. “To all my amazing fans, I will be back in the Asian swing in a few weeks and look forward to finishing the year healthy and strong.”

Sharapova had been the highest-seeded rival in Williams’ half of the US Open draw, a status that now belongs to seventh-seeded Serbian Ana Ivanovic, a possible semi-final foe for the 33-year-old American. Williams is trying to complete the first Grand Slam calendar-year title sweep since Steffi Graf in 1988 and match Graf’s Open Era-record of 22 Slam singles crowns. Sharapova had not played a match since losing to Williams in a Wimbledon semi-final last month because of the injury, which she said had been a day-to-day thing since it happened. “Dealing with these nagging things, it’s almost like a day-to-day process,” Sharapova said on Saturday. “When you are facing something with the body it’s always a day-to-day process.”

Williams is 18-2 all-time against Sharapova and has won their past 17 meetings in a row. Prior to pulling out of the tournament for the second time in three years, Sharapova described the injury as “just a muscle strain”. “I’ve done everything I could to be ready,” Sharapova said. “There’s nothing more that I could have done.”

Sharapova did make the publicity rounds in the days before the US Open, including a photo shoot with a New York taxi and many of her rivals that noted her position at the front, well away from Williams and ex-boyfriend Grigor Dimitrov. “Time-wise it has been the same for me as it has the last seven or eight years,” said Sharapova of her publicity outings.

The 28-year-old Russian had been tweaking her tournament schedule in the past few weeks in order to give herself a chance to come back on the Flushing Meadows hardcourts, knowing that pulling out of tuneup events in Cincinnati and Toronto would hurt her chances in New York. “It’s always the adjustment of being a professional athlete in a sport that requires many weeks out of the year to compete at a high level,” Sharapova said. “Don’t always know where some things come from but sometimes you have to make adjustments to be healthy and ready for the big ones. It only gets tougher as you get older.”