The Swiss legend has never lost any of his 18 opening-round matches at Flushing Meadows and continued his streak with a straight-sets win over his Japanese opponent.
Federer – a five-time US Open winner chasing his first major in New York for a decade – made light work despite the clammy conditions inside the Arthur Ashe Stadium, winning 6-2, 6-2, 6-4.
The 37-year-old was on court for an hour and 52 minutes as he saw off world No 177 Nishioka and despite a late fight-back in the third set, Federer earned a comfortable win.
That was his 83rd overall at the US Open and maintained his fine record of having never lost his first match at the tournament.
And Federer joked that he hopes to continue that winning streak until the end of his career, although said he is not willing to hang his racket up just yet.
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Speaking on court after his win, Federer said: “I’m very happy to be back in New York, healthy – the last couple of years have been difficult so it’s nice to be back, feeling really good.
“I’m happy I never stumbled at the first hurdle. It’s almost time to retire, but not yet!
“I’m happy I played well tonight and Nishioka was a tough opponent, he’s got fast legs and a bright future ahead of him. I was very happy with how I played.”
Sweltering temperatures at the US Open led to several retirements earlier in the day and Federer also visibly felt the conditions as sweat poured off him in his post-match interview.
Acknowledging the difficulty of playing in such heat, the 20-time Grand Slam champion added: “I think it’s particularly tough for us Europeans, we don’t get this type of humidity where we live and grow up.
“It’s something we have to get used to over the years when we’re on tour.
“I had some rough ones earlier in my career where you come out and it’s so humid, the pulse never comes down and you’re sweating so much you don’t know what hit you.
“So I’m happy I’ve gotten used to it but no doubt about it, sometimes you can do whatever you want but you’re just going to cramp up.
“It’s tough so you’re happy when you survive a day like this, no doubt.”
Federer will face Benoit Paire in the second round having won all of his six previous meetings with the Frenchman including at the Halle Open earlier this year.
Federer is looking to improve on his quarter-final finish at the US Open last year and has lost two finals and three semi-finals since his last success here in 2008.