The 24-year-old will compete in the open water race in Beijing
Amputee swimmer Natalie Du Toit will carry the South African flag during the opening ceremony of the Olympics.
"Natalie was the obvious choice for team South Africa," said Hajera Kajee, the head of the team, in Beijing.
No female amputee has competed in the Olympics before and Du Toit will participate in both the Olympic and Paralympic Games.
A lavish ceremony involving about 10,000 performers will open the Beijing Games in China on Friday.
Du Toit qualified for the Olympics by finishing fourth in the 10km open water world championships in Seville in May.
The 24-year-old will compete in the open water race in Beijing before contesting six events at the Paralympics.
She could become the first amputee in 56 years to win a medal at the Olympics.
"It's been a dream for me since I was six years old to go to the Olympic Games and to finally have that dream realised is something massive for me," she says.
She will lead South Africa's contingent of 121 competitors into the Bird's Nest Stadium in Beijing.
Du Toit, who had a left leg amputated after a motorcycle accident seven years ago, competed in both the able-bodied and disability events at the Commonwealth Games in 2002 and 2006
The 10km swim - often described as "wrestling in water" because of its aggressive tactics - will be making its debut at the Games this August.
The event will be watched on TV by an estimated four billion people.