The area around Bethanie originally belonged to the Red Nation. At the beginning of the 18th century the ǃAman, a subtribe of the Orlam people, obtained settlement rights and settled here. As missionaries started travelling north from the Cape Colony in the early 19th century, they established mission stations on their way. The London Missionary Society founded the town, but, because of a shortage of missionaries and presumably because of the cooperation between the London and Rhenish Missionary Society at the time, they instead sent a German. Reverend Heinrich Schmelen arrived in 1814 as missionary of the Kaiǀkhauan and their leader Amraal Lambert. The Schmelenhaus was built the same year, long considered the oldest structure in Namibia. It is a National Monument since 1952 and serves currently as a small museum. It was later discovered that the church and the pastor's house in Warmbad, both destroyed in 1811, were older than the Schmelenhaus, and that the fortification of ǁKhauxaǃnas predates all European constructions. Schmelen also initiated the building of a chapel which was in ruins when James Edward Alexander visited the village in 1837. In 1822, Schmelen left Bethanie after becoming dissatisfied with his missionary work among the local tribes, who refused his repeated and impassioned pleas to attend church and an ongoing conflict between Amraal Lambert's Orlam and another Namaqua tribe living at the station. Livestock and men were killed, and buildings burned. According to James Edward Alexander, Schmelen had "tried in vain to prevent the people of the station exchanging their cattle at ... for fire-arms and ammunition" and saw no end to the local conflicts. The original church was built in 1859, and also still stands today. In 1883, Bethanie was the scene of the historical land sale at the house of Namaqua chief Josef Frederiks II that would eventually establish Imperial Germany colony of German South West Africa. Adolf Lüderitz in May 1883 obtained the area of Angra Pequena from Frederiks for 100£ in gold and 200 rifles. Three months later on 21 August, Frederiks sold Lüderitza stretch of land wide, between the Orange River and Angra Pequena, for 500£ and 60 rifles. This area was far bigger than Frederiks had thought, as the contract specified its width as '20 geographical miles', a term that the tribal chief was not familiar with: 1 German geographical mile equals, whereas the common mile in the territory was the English mile, 1.6 kilometres.
A fictionalized version of Bethanie – named "Bethany" in English and depicted as a drought-plagued former mining town – is the primary setting for Richard Stanley's 1993 feature horror film, Dust Devil.
