Pistorius, 25, had both legs amputated between the knees and ankles when he was 11 months old.
He has competed in the prior Paralympic Games and his bid to run in the Olympics gained notoriety when the International Association of Athletics Federation (IAAF) ruled prior to the 2008 Games that his artificial legs gave him a competitive advantage.
That ruling was overturned, however, by the Court of Arbitration for Sport and he qualified for this year's South African team.
Pistorius appeared at Olympic Stadium Saturday in the first of seven qualifying heats for the 400 heats and he ran second in the time of 45.44. The top three finishers in each heat plus the next three fastest qualified for the next round of running, which will take place on Sunday. The finals will be held Monday.
"I didn't know whether to cry," Pistorius said. "I had a mixture of emotions. It was the most amazing experience, the crowd was amazing."
While Pistorius moved on to the next round, defending 400-meter champion LaShawn Merritt of the United States did not. He pulled up lame while running in the sixth heat.
The fastest time in 400 qualifying was the 44.43 turned in by Jonathan Borlee of Belgium.
There were 13 times faster than that of Pistorius. He must be among the fastest eight in the next round to reach the gold medal race.