The US Tennis Association said the 2009 champion from Argentina -- who was runner-up at Flushing Meadows in 2018 -- will miss the tournament as he continues his recovery.
Del Potro shared a video of himself walking on a treadmill on July 31.
On June 21 he had said he would undergo surgery after breaking the patella in his right knee for the second time in nine months. At that time he said he didn't know if he'd played his last match.
So it's no surprise he won't be at Flushing Meadows; the USTA's announcement merely made it official.
Del Potro's withdrawal sent American Denis Kudla -- who was previously announced as a wildcard -- into the main draw. The USTA gave that wildcard to American Christopher Eubanks.