Top-ranked Novak Djokovic cruised into the second round of the US Open on Monday while Japanese fourth seed Kei Nishikori crashed out after his runner-up effort last year.

And three-time defending women’s champion Serena Williams, the world No.1 trying to complete a calendar Grand Slam, saw three top rivals fall as she prepared for her opener later at Arthur Ashe Stadium.

Djokovic needed only one hour and 11 minutes to capture a 6-1 6-1 6-1 victory over Brazil’s Joao Souza.

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“There’s something I love about number one for sure. Hopefully I can keep it up,” said Djokovic.

“I’m just hoping I can continue to play this way and if I can, I feel I have a really good chance against anybody.”

Djokovic’s highest-ranked possible semi-final foe had been Nishikori, but last year’s US Open runner-up exited the US Open at the first match for the third time in five years as France’s 41st-ranked Benoit Paire saved two match points and defeated the Japanese star 6-4 3-6 4-6 7-6 (8/6) 6-4.

“To beat Nishikori, for me, it was impossible to imagine this,” Paire said. “I’m really happy.”

Top-10 women’s seeds Ana Ivanovic, Karolina Pliskova and Carla Suarez Navarro exited with opening-match losses, leaving 12th seed Belinda Bencic as the top-rated foe in Williams’ half of the draw.

Williams, who lost to Bencic in the Toronto semi-finals, could face the Swiss teen again in the quarter-finals as she chases the first calendar Grand Slam since Steffi Graf in 1988 and a 22nd career major title to match Graf’s Open Era record.

Williams opens at night against Russia’s 86th-ranked Vitalia Diatchenko followed by Spanish eighth seed Rafael Nadal, a possible quarter-final foe for Djokovic, facing Croatia’s Borna Coric, who won their first meeting last year at Basel.

Paire, who had never before beaten a top-five foe, 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 No.1.

“He was very aggressive, so there were many rallies and it was tough to get rhythm,” Nishikori said.

Nishikori enjoyed his highest seed for any Grand Slam event all-too briefly, walking off Louis Armstrong Stadium with his head down.

Nishikori led the tie-breaker 6-4 but swatted a forehand long, watched Paire smack two service winners and then Nishikori netted a forehand to force a fifth set.

Paire, who won his first ATP title last month at Bastad, broke for a 3-2 lead and held to the finish to win after three hours and 14 minutes.

“To be honest, I think I’m lucky,” Paire said. “Today, for me, it’s a good day. I’m really happy to win.”

Nishikori had won three titles this year, including a US Open warm-up win at Washington that saw him avenge last year’s US Open final loss to Croatian Marin Cilic.

“It’s very sad always to lose first round,” Nishikori said. “I think it was more because of him I wasn’t playing 100 per cent.”

Cilic won his opener 6-3 7-6 (7/3) 7-6 (7/3) over Argentine qualifier Guido Pella.

There was bad news for the Australians, with Daria Gavrilova, Casey Dellacqua, Matt Ebden and John Millman all bundled out.

Unable to capitalise on Maria Sharapova’s injury-enforced withdrawal, Gavrilova fell 6-2 4-6 7-5 to Russian teenager Daria Kasatkina.