Potchefstroom University developed out of the Theological School of the Reformed Churches in South Africa (Gereformeerde Kerke in Suid-Afrika in Afrikaans, abbreviated as GKSA), which was founded on 29 November 1869 in Burgersdorp, Cape Province.

[1] At the founding meeting, it was decided that education would also be offered to prospective teachers and to persons without any particular profession in mind.

In 1877 a "Literary Department" was established, with one professor, with the specific aim of educating students for academic degrees or as teachers.

In order to qualify for government subsidies, the Literary Department was separated from the Theological School in 1919 and the Potchefstroom University College for Christian Higher Education (Het Potchefstroom Universiteitskollege voor Christelijk Hooger Onderwijs in Dutch, and usually abbreviated as PUK) came into being.

The Vaal Triangle Campus of the university was established in Vanderbijlpark in 1966 in order to provide that area with tertiary education.