The Wimbledon champion is sitting out his second grand slam of the season because of his ongoing refusal to be vaccinated against Covid-19.
Djokovic waited until the eve of the draw on Thursday to withdraw, having finally given up hope that the US Government would relax restrictions in time.
The Serbian's absence strengthens Nadal's hopes of adding a 23rd grand slam title to his collection, which would again see him move two clear of Djokovic in the all-time standings.
But the Spaniard would rather his rival was in New York, saying: "From my personal perspective, it's very sad news. It's always a shame when the best players of the world are not able to play a tournament because of injuries or because of different reasons.
"In this case, not having one of the best players of the history in the draw of a grand slam is always an important miss. It's tough for the fans, tough for the tournament. In my opinion, tough for the players, too, because we want to have the best field possible.
"But, on the other hand, I repeat what I said plenty of times: the sport in some ways is bigger than any player.
"I missed a lot of important events in my tennis career because of injuries. Last year I was not here. Two years ago I was not here. The tournament continues. The world of tennis keeps going."
Nadal is back in New York for the first time since winning his fourth title here in 2019 having chosen not to travel in 2020 and then missed out with a foot problem last year.
He is yet to lose a best-of-five sets match this season but is short on match practice having only competed once since being forced out of Wimbledon ahead of the semi-finals by an abdominal tear.
Nadal remains cautious of the scar tissue left by the injury but is happy with the form he has been showing in practice.
The 36-year-old, who will take on Australia's Rinky Hijikata in the night session on Tuesday, said: "It's a tough injury because it's dangerous, it's risky. When you have a scar, it's a place that you put in a lot of effort when you are serving. You need to find flexibility again.
"I am doing things the best way that I can. I hope to be ready for the action. That's the only thing that I can say. With the tools that I have today, I hope to be competitive enough to give myself a chance.
"I'm taking care with the serve. But, in general terms, I am practising at a high level of intensity. I'm quite happy the way that I am playing."