Born in Vryburg, South Africa, to Greek parents, Penny Siopis pursued her formal art education at Rhodes University, completing her master's degree in 1976. She furthered her studies at Portsmouth Polytechnic in the United Kingdom before embarking on a long-standing career in academia, holding positions at Technikon Natal, the University of the Witwatersrand, and the Michaelis School of Fine Art at the University of Cape Town.

Her work is characterized by a diverse use of media, including oil painting, found objects, and experimental film. She frequently engages with the concept of the archive, utilizing personal and historical narratives to examine the complexities of the South African experience and the nature of collective memory.

Siopis has received significant academic recognition, including an honorary doctorate from Rhodes University. She continues to contribute to the field as an honorary professor, maintaining a practice that bridges historical inquiry with contemporary visual expression.