Onyewu out for up to four months
Onyewu landed badly after jumping for a header and immediately called for assistance. He was taken off the field on a stretcher and later found to have torn a patellar tendon in his left knee.
Onyewu, who plays for Italy's AC Milan, should recover in time for next year's World Cup finals but his injury is another blow to the United States a day after forward Charlie Davies was seriously injured in a car accident in suburban Washington.
Davies, who suffered a broken leg among other injuries, remains in hospital and is almost certain to miss the finals.
"We've had two days of tough news," said Bradley.
"'Guch' is such an important part of our team. He's young, he's healthy. Our doctors are good but nonetheless, it's another setback for us," he said.
The United States finished top of the CONCACAF group qualifying for South Africa along with Mexico and Honduras.