Novak Djokovic's bid for a 10th grand slam title received a double boost as the Serb thrashed Brazil's Joao Souza in the US Open first round shortly after fourth seed Kei Nishikori crashed out.
Nishikori, who beat Djokovic in New York last year, was due to meet the world number one again in the semi-finals but the Japanese lost in a five-set thriller to France's Benoit Paire.
Paire, ranked 41st in the world, saved two match points in the fourth set before claiming a decisive break in the fifth for a shock 6-4 3-6 4-6 7-6 (8/6) 6-4 victory.
It means the highest seed left in the top half of the draw besides Djokovic is Spain's David Ferrer, who has failed to beat Djokovic in his last nine attempts.
US Open 2015 in pictures
US Open 2015 in pictures
1/4 First Round
Novak Djokovic celebrates his victory over Joao Souza
2/4 First Round
Serena Williams consoles Vitalia Diatchenko after beating her in the US Open
3/4 First Round
Heather Watson suffered an early exit to Lauren Davis in a 7-6 7-6 defeat
4/4 First Round
Kei Nishikori lost to Benoît Paire 6-4 3-6 4-6 7-6 6-4
For Paire, the win was arguably the finest of his career and the talented Frenchman will now play Turkey's world number 84 Marsel Ilhan to reach the third round for the first time.
"It was impossible for me to imagine this, beating Nishikori," Paire said.
"I will celebrate this with my coach, my team and my family. I am very happy."
Paire later added: "When I saw the draw against Kei I said, 'bad luck'.
"You play Kei first round, he made the final last year. The thing is you have to have pleasure in this match. You have to feel good on court, to have fun. You're going to play on a big court, in a big stadium.
"My coach told me the most important thing is when you go out on the court, you win, you lose, you don't care, just have fun."
Nishikori reached the final 12 months ago when he lost to Marin Cilic but has struggled for similar success since, losing in the quarter-finals at the Australian and French Opens this year before a second-round exit at Wimbledon.
"It's always very sad to lose but he was playing good tennis," Nishikori said.
"I don't think I played badly. I didn't play great but it's never easy in the first match. He's a good player."
Djokovic never looked like following Nishikori out of the tournament as he took just one hour and 11 minutes to beat Souza 6-1 6-1 6-1.
The top seed arrived with question marks hanging over his form following defeats to Andy Murray in Montreal and Roger Federer in Cincinnati but he believes he sent out a clear message to his rivals.
"I couldn't ask for a better opening of this year's US Open," said Djokovic, who now plays Austrian Andreas Haider-Maurer in round two.
"A dominant win like the one today, it adds to your confidence, your self-belief. But it's also making a statement for everybody that is out there watching.
"We are all watching each other's matches. It's important you're out on the court with the right intensity and you're sending a good message, and I've done so."
Haider-Maurer beat Canada's Vasek Pospisil 6-4 3-6 6-7 (0/7) 6-0 6-1.
There was also a morale-boosting victory for eighth seed Rafael Nadal, who has struggled for form this year but overcame the talented Borna Coric 6-3 6-2 4-6 6-4.
"The first two sets were a very high level for me and I was happy with how I played," Nadal said.
"I got a little bit tired, the conditions were very humid, but I was able to play aggressive again in the fourth set so I am very happy."
Defending champion Cilic had no problem against Argentine qualifier Guido Pella, winning in straight sets, while Ferrer, Jo-Wilfried Tsonga and Milos Raonic are also safely through.
France's Gael Monfils is, however, out. The Frenchman, seeded 16th, was losing 6-2 4-6 5-0 to Ukraine's Illya Marchenko when he retired injured.