The town, founded in 1838 by the Voortrekkers, is the second oldest settlement of people of European descent in the thenTransvaal. The honour of oldest European settlement belongs to Klerksdorp, situated approximately 40 km (25 mi) to the West. This is sometimes challenged by historians because the first settlement was in the "upper regions of the Schoon Spruit", which might be between Klerksdorp and Potchefstroom. Potchefstroom however was the first to develop into a functional town.
For a short time until 1840, the towns of Potchefstroom and Winburg as well as their surrounding territories were joined in a political entity known as the Republic of Winburg-Potchefstroom. Voortrekker leader Andries Hendrik Potgieter was elected as chief commandant.
In October 1840, after a meeting between Potgieter, Andries Pretorius and G.R. van Rooyen it was decided that Potchefstroom would unite with "Pieter Mouriets Burg" (Pietermaritzburg).
In 1848 Potchefstroom became the capital of the ZAR, a status which was affirmed by Britain in 1852.
Over 16 and 17 January 1852, the Sand River Convention was signed between Andries Pretorius representing the Boers and Major W.S Hogge and Mr C.M. Owen representing Britain. According to this convention the British Government would allow the emigrant farmers north of the Vaal river to govern according to their own laws, with a policy of non-interference from both sides - slavery in the north was also prohibited under this agreement. This signalled the establishment of the Zuid Afrikaanse Republiek (ZAR) (South African Republic in English). In article 17 of the Constitution of the ZAR of 18 February 1858 (which was accepted in Rustenburg), it was stated that "Potchefstroom, located on the Mooi River, would be the capital of the Republic and that Pretoria would be the seat of government". In May 1860 Potchefstroom became the "chief city" of the Republic, with the capital having moved to Pretoria.