Nishikori, last year's runner-up, upset by Paire at US Open

Benoit Paire of France hits a forehand against Kei Nishikori (not pictured) of Japan on day one of the 2015 US in New York, USA, Aug 31, 2015. [Photo/Agencies]

The 25-year-old followed that up with more success in 2015 and came into the US Open with his first top-four seed at a Grand Slam tournament. He made it to the quarterfinals at both the Australian and French Opens this year, but withdrew from the second round at Wimbledon because of a calf problem, the latest injury in a career plagued by them.

He had been playing well on the hard courts this summer before pulling out of Cincinnati, though, winning the title at Washington and beating Rafael Nadal in Montreal, where he lost to eventual champ Andy Murray in the semifinals.

It's the first time since 1999 that a US Open men's finalist lost in the first round the following year. Cilic had no such problems Monday, starting his title defense with a straight-set victory over 94th-ranked qualifier Guido Pella.

The 26-year-old Paire has never been past the third round at a major tournament. He had 21 aces Monday, the last to close out the match.

Novak Djokovic and Rafael Nadal were playing later Monday.

On the women's side, four of the top 10 players are already out, with seventh-seeded Ana Ivanovic, eighth-seeded Karolina Pliskova and 10th-seeded Carla Suarez Navarro losing Monday, a day after third-seeded Maria Sharapova withdrew. All were on Serena Williams' half of the draw.

Williams opens her pursuit of the first Grand Slam since Steffi Graf in 1988 on Monday night in Arthur Ashe Stadium. Before she even steps on the court, not a single top-10 player stands in the way between the American and the final.