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U.S. equalized at the 63rd minute on Donovan's spot kick, which was awarded after Clint Dempsey was brought down by Jonathan Mensah in the penalty area after breaking through Ghana's defense.
Donovan smashed the penalty shot on the inside of the post to deflect into the net.
"I really felt when we got to 1-1 there were some chances for us," United States coach Bob Bradley said. "Early in the overtime we go down again early. At that point, with everything we put into the game early, we didn't have enough after that."
At the 75th minute, unmarked Michael Bradley raced through between two defenders into the area to smash the ball at goal, which was saved by well-positioned Kingson.
Five minutes later, Jozy Altidore stormed into the area and fell down while muscling with Anthony Annan. Before hitting the ground, the American forward delivered a shot which went half meter wide of the post.
Uruguay, two-time world champions,reached the World Cup quarter-finals for the first time since 1970.
The Taeguk Warriors played brilliantly in the rain-drenched Nelson Mandela Bay Stadium and equalized on Lee Chung-Yong's header in the second half, but Suarez's second goal, converted in a spectacular way, ended the Asian side's heroic run in South Africa.
A shameful record, in which Asians have never beaten South Americans in the World Cup, will last - at least until Japan's second round clash with Paraguay.
Uruguay coach Oscar Tabarez made a notable change with Diego Godin replacing Mauricio Victorino at the back, while his counterpart Huh Jung-Moo threw in winger Kim Jae-Sung in place of Yeom Ki-Hun.