The town was founded in 1867 on the banks of Jammersbergspruit, a tributary of the Caledon River, and named for Louw Wepener who was killed in 1865 while trying to storm Moshweshwe's stronghold of Thaba-Bosiu in the Free State's second war against the Basotho.
Wepener was the southern most of several settlements founded by the Free Stater's in the `conquered territories' to prevent the Basotho from resettling the land taken from them during the war of 1865.
The Dutch Reformed parish was established in 1870 and the town was granted its first management board in 1875.
Today the town is a commercial centre for a 1 725 square km district where mixed farming is practised (cattle and sheep ranching, dairying, wheat and maize)
The district of Wepener was the scene of many battles, raids and skirmishes during the 19th century. Many graves, mostly without identification, are sad reminders of the events in the valley of Jammerbergspruit during this stormy period.
During the Anglo-Boer War a British garrison of 2000 men under Col EH Dalgety was attacked by General Christiaan de Wet at Jammersdrift on the Caledon River.
The siege lasted 17 days - until reinforcements arrived on 25 April 1900 to end the battle in favour of the British.