PHOTO: AFP
The year's final Grand Slam tournament began with drama on the Flushing Meadows hardcourts as 41st-ranked Frenchman Benoit Paire saved two match points and rallied to defeat Nishikori 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.
Three-time defending champion Williams, who lost to Bencic in a Toronto semi-final, could face the Swiss teen again in the quarter-finals.
Williams is chasing the first calendar Grand Slam since Steffi Graf in 1988 and a 22nd career major title to match Graf's Open Era record. She opens against Russia's 86th-ranked Vitalia Diatchenko.
Williams and former US Open winners Novak Djokovic and Rafael Nadal were set for later matches at Arthur Ashe Stadium.
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 number one.
"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 after his third first-round exit in New York in five years.
Nishikori led the tie-breaker 6-4 but swatted a forehand long, watched Paire smack two service winners and then 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 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 included 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 percent."
Cilic won his opener 6-3, 7-6 (7/3), 7-6 (7/3) over Argentine qualifier Guido Pella.
On the women's side, Slovakia's 50th-ranked Dominika Cibulkova ousted seventh-seeded Ivanovic 6-3, 3-6, 6-3, delivering the Serb star's first US Open first-match exit 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."
After the injury-forced withdrawal of Russian third seed Maria Sharapova, Ivanovic had been Williams' top-ranked rival.
That status fell to Czech eighth seed Pliskova, who lost to American Anna Tatishvili 6-2, 6-1, and to 10th seed Suarez Navarro, who lost to Czech Denisa Allertova 6-1, 7-6 (7/5).
"My return (was crucial)," Tatashvili said. "I felt the ball really well. I was trying to get as many first serves back as possible."
One Williams rival who advanced was her older sister Venus, a seven-time Grand Slam champion and US 23rd seed who outlasted Puerto Rico's Monica Puig 6-4, 6-7 (7/9), 6-3. Venus could play Bencic in round three.
World number one Djokovic meets Brazil's Joao Souza while Spanish eighth seed Nadal, a possible quarter-final foe for Djokovic, faces Croatia's Borna Coric, who won their first meeting last year at Basel.
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