Pistorius, who earlier this month became the first double-amputee to compete in the Olympics, stormed to victory in his heat at the Olympic Stadium in east London, clocking a new best of 21.30sec.
The 25-year-old said he was happy with the time — and the reception from the 80,000-strong crowd — but again played down expectations that he would complete the sprint clean-sweep.
“I’ve done a world record tonight, so we’ll see what happens, but the 100m isn’t really my event,” he told reporters.
Pistorius, nicknamed the “Blade Runner” because of his carbon fibre prostheses, will face Beijing silver medallist Jim Bob Bizzell, as well as his long-standing rival Jerome Singleton, both of the United States.
The race had been billed as the highlight of the evening’s programme, with Pistorius’ participation in the 400m heats and 4x400m relay final at the Olympics making him the most high-profile athlete at the Games.
But Irish sprinter Jason Smyth gave a stunning performance in the T13 100m, streaking to victory in 10.46sec, breaking the previous world best of 10.54sec that he set in qualifying on Friday night.