The exhibition follows the 88-year-old painter and mural artist's unusual trajectory from rural South Africa to global acclaim. After Cape Town, it will be taken on an international tour.
Despite having no formal art training, Mahlangu earned an international reputation with works referencing her Ndebele heritage and using skills passed down for generations.
"It's in my genes to paint Ndebele," the artist, wearing traditional, brightly colored blue, yellow and brown garments and jewellery — and white sneakers — told AFP in an interview.
Mahlangu learned the art of Ndebele design as a child from her mother and grandmother.
With just a chicken feather, she first painted mud huts and chipboards before moving on to luxury cars, vodka bottles, skateboards and footwear as her intricate patterns became huge commercial hits.
"The Ndebele art is within me, I was born with it. It is important for me, I don't pretend to love it, I love it," she said.
The retrospective, which opened at the Iziko South African National Gallery on Sunday, features pictures, a short film and more than 100 contemporary works.
Among them is Mahlangu's iconic BMW Artcar -- a sedan she painted with her trademark colorful geometric shapes in the 1990s as part of a collaboration with the German carmaker.
Yet the artist said she was hard-pressed to pick her best work. "I love everything I have painted, everything! I have no favorite," she said.
Mahlangu's first big international break came in 1989, when she was 54.
Her ornately decorated house had caught the eye of French researchers who invited her to the Pompidou Center.
However, South Africa was not quick to recognise Mahlangu's talent — she gained international prominence at a time when the art scene in her home country was focused on contemporary styles.
"The retrospective pays homage to Dr. Mahlangu's unique approach to art, which intersects African culture with modernity and the contemporary, symbolising pride, self-determination and innovation," said curator Nontobeko Ntombela.
After Cape Town the exhibition will move to Johannesburg's Gauteng province before departing for the United States and beyond.