The defending champion, who beat Stanislas Wawrinka in the last round, takes on the Argentine at Flushing Meadows this evening for a place in the semi-finals.
"Del Potro is a quality player, somebody that when he's physically fit he can challenge anybody on any surface," Djokovic said.
"It's quarter-finals. There is no really clear favourite anymore. I have to try to play my best."
The pair recently met in the bronze-medal match at the London Olympics, with Del Potro winning that contest in straight sets.