Nearby localities include Kafr Shams to the northwest, Deir al-Bukht to the north, Jabab to the northeast, Bassir to the east, Tubna to the southeast, Inkhil to the southwest and Qayta to the west.

Sanamayn has been identified with the Roman-era village of Aere,[5][4][6] a station mentioned in the Antonine Itinerary on the road between Damascus to the north and Nawa to the south.

[5][6] Another was apparently dedicated to Tyche's Roman equivalent, Fortuna, who was central to Bosra's state cult; it dates from the early to mid-3rd-century CE, during the reign of emperor Septimius Severus.

[7] Sanamayn has also been associated with Bathyra, a village situated on the border between Batanaea and Trachonitis, where circa 7 BCE Herod established a Jewish Babylonian military colony under the leadership of Zamaris to safeguard the area from local brigands.

[14] The place was visited by medieval Syrian geographer Yaqut al-Hamawi in the 1220s during Ayyubid rule, and noted it was "a town in the Hauran, 2 marches from Damascus.

[6] As in other towns on the Hajj (Muslim pilgrimage to Mecca) caravan route, the Ottoman sultan Selim I constructed a fortress in al-Sanamayn sometime between 1516 and 1520.

[17] In 1596 the town appeared in the Ottoman tax registers as Sanamayn and was part of the nahiya (subdistrict) of Bani Kilab in the Hauran Sanjak.

The villagers paid a fixed tax-rate of 20% on various agricultural products, including wheat, barley, summer crops, goats and beehives, in addition to on a water mill.

[dubious – discuss][4] During roughly the same time period it was reported by the Royal Geographical Society that al-Sanamayn was an entirely Muslim village with about 60 houses and with an entrance marked by large basalt blocks.

[19] It belonged[clarification needed] to a Turkoman family known as Kawwas-oghlu who maintained encampments between the town and Khan Dannun to the north.

Al-Sanamayn was "well supplied with water," contained several bird species and its pools were filled with leeches which would be collected and sold in the markets of Damascus.

[26] Activists alleged that on 18 September an eleven-year boy was killed after being shot in the head by security forces during a boycott protest by students in al-Sanamayn on the first day of the 2011–2012 school year.