The monastery is situated in the isolated valley of the Vere river in Kvemo Kartli. The name of the monastery originates from the name of village Bethany in Palestine, which is recorded in the New Testament as the home of Mary, Martha and Lazarus.
Not much of the history of the monastery is recorded in Georgian historical tradition. It was a familial abbey of the House of Orbeli. The Orbeli were temporarily dispossessed of their estates by the royal crown at the end of the 12th century, but their later offshoot, the Gostashabishvili family, happened to have been the monastery's owners in early modern Georgia.
A number of invasions in the history of Georgia depopulated and half-ruined the monastery. It was restored in the 19th century, due to the efforts of Hieromonk Spiridon Ketiladze who resigned as an abbot in 1922. Though unofficially, Betania was the only operating Georgian monastery till 1963 when it also became defunct for the next 15 years. In 1978, the energetic Patriarch of Georgia Ilia II obtained permission from the Soviet authorities to reopen the monastery. Some years later, the cloister was refurnished and the local monastic community grew in size and power.