World number two Nadal was forced to withdraw from the final grand slam of the season after sustaining a wrist injury, leading many to tip Djokovic as the man most likely to triumph at Flushing Meadows.
But Djokovic, coming off the back of beating Roger Federer in the Wimbledon final last month, does not share that view, and believes the field is more competitive than ever before.
"When Rafa is not around it changes everything," said the world number one as he spoke to the press on Saturday. "But, on the other side, we have all the other best players in the world here.
"Favourites? I leave it to the people. Really, I'm not thinking about it. Everyone is starting from scratch. It's very open."
Djokovic - seeking his eighth grand slam title, and his second US crown - has hardly enjoyed ideal preparation for the tournament, losing in the last 16 in both Cincinnati and Toronto in recent weeks.
And he acknowledges that the standard of tennis being played by his rivals is better than ever, with a new-found depth in the men's game.
"Nowadays, the competition level is higher. You have players around 15 and 20 in the world, and the quality of the tennis they are playing is higher than five years ago, in my opinion. That makes it hard to win this tournament.
"The biggest reason is the game has become more physical. My coach Boris [Becker] won Wimbledon at 17.
"Today it is very difficult to do anything like that. It has changed significantly. It takes some years to get to the stage where you feel you are actually complete."