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The South African was dominant down the home straight, finishing in 21.67 seconds, almost a second clear of Jim Bob Bizzell from the United States, with Britain's Ian Jones in third.
"This race is definitely going down as one of my best ever races. I've never run in front of a crowd this big and just the crowd, the athletes, it was an awesome race and I couldn't have hoped for anything better," he said.
The 21-year-old said he had been feeling a little unwell in the run-up to the final, but that adrenaline saw him home.
"This is definitely one of the most amazing nights ever. It's really been a good memory," he said.
Pistorius has just one race left, the 400m, in which he is targeting a world record.
"I'm really looking forward to the 400m. If those two races, if it goes like that, then I'll be extremely happy," said the South African, the world record holder in his category in all three events.
Nicknamed after the carbon fibre blades he wears, Pistorius won a court battle to take part in the Olympics after proving himself a strong competitor against able-bodied athletes.
He eventually failed to qualify for the Beijing Olympics, blaming in part the distraction of his court battle, but he is targeting the London 2012 Games. Among his best achievements against able-bodied athletes was a second in the 400m event at the 2007 South African national championships.
