The lyrics will combine English and Xhosa and the opera will feature a 60-piece orchestra performing western and traditional African music.
It is believed to be the first opera fully composed and orchestrated in the country.
The cast will be revealed in January.
The opera is due to premiere at the State Theatre in Pretoria on April 28.
Three years ago, Canada denied Mandikizela-Mandela a visa application to attend the premiere of an opera about her life — called The Passion of Winnie — in Toronto.
The new show combines the same team of South African-born composer and musician Bongani Ndodana-Breen and filmmaker Warren Wilensky.
Winnie Mandikizela-Mandela came to attention in 1964 when her then husband Nelson was sentenced to life imprisonment. She was arrested in 1969 for printing and distributing anti-apartheid literature.
She separated from her husband in 1992 amid stories of her infidelity and the couple divorced in 1996.
In 2003, she was found guilty on charges of fraud and theft.
Earlier this year, the BBC screened a dramatisation of her life, starring Oscar-nominee Sophie Okonedo in the main role.
Hollywood actress Jennifer Hudson has also taken on the same role in a film due for release next year. — BBCOnline.