Mpe was born in Limpopo, a rural South African province. At the time of his birth, South Africa was under the Apartheid State. In 1989, at 19, Mpe moved to Johannesburg to study African literature at the University of the
Witwatersrand (Wits). As a student, Mpe lived in the inner-city neighborhood of Hillbrow, which would become the setting of his one published novel,
Welcome to Our Hillbrow. After graduating from Wits, Mpe went abroad and received a diploma in publishing from the polytechnic school Oxford Brookes in England, after which he returned to South Africa and the University of Witwatersrand for a master’s degree. Following his MA, Mpe became a professor in African Literature at Wits. Mpe spoke and read both English and Sepedi (both national languages of South Africa), although the majority of his published work is written in English. In 2003, Mpe began a doctorate at the university in sexuality in post-apartheid South African literature. However, he left this degree unfinished to instead train as a
ngaka—a traditional healer. Mpe died rather suddenly at 34 from a disease that was never conclusively diagnosed. In his writing, Mpe engaged with the political issues of his time South Africa, such as the aftereffects of apartheid and colonialism, prejudice within Black South African communities, the divide between rural and urban communities, and biases and misunderstandings about AIDS.