The South African team never made it to the third section of the 4x400-meter relay in the opening heat after Ofentse Mogawane crashed, leaving Pistorius waiting in the changeover zone for a baton that never came.
When he realized his Olympics were over, Pistorius raised his hands to his head, and waved his arms down in frustration. Since the South Africans had already won silver at the world championships last year, the "Blade Runner" knew his team had a good chance of mounting the Olympic medal podium after Friday's final.
"It's not the place you want something like this to happen," Pistorius said.
Now he leaves London with only the distinction of becoming the first amputee athlete to run in an Olympic track and field competition.
His exit, though, was tough to deal with.
"It's frustrating. It's so hard. You have so much support from back home," Pistorius said.
Mogawane and Kenya's Vincent Kiilu tangled heading into the home straight of the second leg of the relay and the South African runner fell to the track, holding his shoulder in pain.
Pistorius still held his hand out for several seconds, seemingly unclear about what happened, until it slowly dawned on him he would no longer get a chance to run.
"Just really disappointing for us because we came off a second place last year at the word champs in a national record," Pistorius said. "We're all pretty battered,"
Together with anchor runner Willem De Beer, he tried to walk over to his injured teammate but track officials held them back. Pistorius was left to applaud Trinidad and Tobago, which won the heat, ahead of Britain.
Beyond South Africa and Kenya, Jamaica was another medal contender failing to reach the final after Germaine Gonzales slowed to a walk and sat on the track, holding his left hamstring. Australia and Germany also failed to go through.
For Pistorius, the early exit happened in the blink of an eye.
He had been looking at the giant screen to follow the progress of the race and when he turned to get set in position to receive the baton, the collision had already happened.
"Things do happen in relays and just sorry it had to happen on a day like this," he said. "I feel sorry for my teammates,"
The Bahamas won the second heat ahead of the United States.