The final Grand Slam of the year kicks off on Monday (28 August) as new world number one Nadal will look to keep his place at the summit of tennis while Federer will be aiming to overtake his long-time rival in the rankings with a victory at Flushing Meadows.
When the draw was revealed, the major talking point was the fact that the duo could meet each other in the semi-final.
Despite having faced each other 37 times over the years, the pair have somehow never faced each other in New York and a potential meeting would be their fourth of the calendar year so far.
Nadal has lost to the Swiss ace on all three occasions so far and understandably prefers not to face Federer.
"If I am in semi-finals, not, I prefer to play against another one," the Spaniard said as quoted on ESPN when asked if he wanted to face Federer. "Is obvious, no? I am not that way [to want the matchup]. Sounds very good, but the real thing, I prefer to play against another player, an easier one if it's possible."
"I know you want to hear the other way, that I would love to play with him. No, of course I understand that [it's] gonna be great for our history. Is true that we played in all [the other] Grand Slam finals.
"We never played here and for sure this year we are not going to play in finals. Finals are more special than semifinals, in that case. Anyway, meeting him here in semifinals with Roger, if that happens that will be something great and amazing. But as I say before, we made a lot [before]."
As for Federer, the 19-time Grand Slam winner is open to the idea of playing Nadal in New York, more so, due to the fact that it has never happened in the US Open before.
"I mean, I'd be happy to play him here," Federer stated as he looks to win a third Grand Slam of the year. "We never played here in New York, so I think that would be fun for everybody involved."
"I mean, there is, like, I don't know, 60-plus players in between us that don't agree in our section that we should make it to the semis. We have our work cut out there.
"But, you know, I'd love to play Rafa here in New York. Hopefully it will be a night session. Hopefully that would be a great atmosphere and one again where we play great like at the Australian Open."