The history of Wepener dates back to the 19th century, when the Boers, led by Louw Wepener, attacked the Basotho nation’s stronghold of Thaba-Bosiu in the Free State. This was the province’s second war against the Basotho, and Wepener died during this battle. The town was named after him after its establishment in 1867.
Wepener was to the south of several settlements, which were known as the ‘conquered territories' to prevent the Basotho from resettling the land taken from them.
In 1870, the Dutch Reformed Church established a parish in town, and a management board was set up in 1875. Wepener would be the scene of many battles during the late 19th century, and the unmarked graves on the outskirts of town are remnants of this tumultuous period.
A city hall was built in 1927, and during the Anglo-Boer war a battle ensued between the British and the Boers at Jammersdrift on the Caledon River.