In 2000, Winfrey pledged $10 million for the facility for 150 girls to former President Nelson Mandela, but has since spent $40 million on the school in Henry-on-Klip, southwest of the capital, South Africa's Independent Online reported. The school will eventually have 450 students, the BBC said.
The school sits on 50 acres, and has 28 buildings that house hi-tech classrooms, computers and science laboratories, the BBC said.
Winfrey reportedly personally interviewed many of the 3,500 applicants from families whose incomes are less than $700 per month, the report said.
The school will open for classes on Friday.
Notable deaths of 2014 [PHOTOS]
Polly Bergen, Emmy Award-winning actress, dies