The monastery, situated in the mountains to the southeast of Melitene and named after the 5th-cent. ascetic Barṣawmo, rose to prominence as the regular residence of Syr. Orth. Patriarchs in the 11th–13th cent., the period often referred to as the Syriac Renaissance. The ruins of the fortified monastery have been located around a peak 1600 m high at the south-western end of the Kaplı Dağı, above the village of Peraş (1300  m) in the upper valley of the Kâhta Çayı and approximately 20 km. to the northeast of Nemrut Dağı, the site of the ancient sanctuary built by Antiochus I of Commagene (70–38 BC), whence the materials may have been brought that were used in the construction of the vaults of the new church of the monastery in 1186 (Honigmann, 49).

The original monastery founded by Mor Barṣawmo probably lay at the foot of the mountain near the Kâhta Çayı. The ‘upper’ monastery must have been built before 790 when Patr. Giwargis of Bʿeltan is said to have ascended there to die. After the large-scale movement of Syr. Orth. Christians into the area around Melitene in the 10th cent., Patr. Yuḥanon da-Srigteh (965–986) and Athanasios Ṣalḥoyo (987–1003) normally resided at the Monastery of Barid, which was probably located near the River Giḥun (Ceyhan) some way to the west of Dayro d-Mor Barṣawmo, but Athanasios is recorded as having died in Dayro d-Mor Barṣawmo, and was succeeded by Yuḥanon bar ʿAbdun (1004–31), a monk of that monastery. Patr. Dionysios IV (1032–42) was forced to seek refuge in Amid because of persecution by Chalcedonians, and, with the exception of Athanasios  Ḥoye (1058–63), his immediate successors normally resided outside areas under Byzantine rule, but with the weakening of Byzantine control in the wake of the Battle of Manzikert (1071), Dayro d-Mor Barṣawmo and the surrounding region became once again the center stage of Syr. Orth. activities. Among the patriarchs from that period, Basilios III (1074–75) and Athanasios bar Kamore (1091–1129) were monks of Mor Barṣawmo. It is reported that measures were taken to strengthen the fortification of the monastery in 1101 and 1164, measures which were necessitated by the attraction that the monastery with its relic of Barṣawmo and its wealth exerted not only on pilgrims but also on less welcome visitors, as well as by its precarious position on the border between Frankish and Armenian territory to the south and Turkish territory to the north. Among the events from the middle of the 12th cent., mention may be made of the plunder of the monastery by Count Joscelin II of Edessa in 1148 and the synod held there in 1155 under Athanasios VI bar Qeṭreh (1138/9–66). The monastery saw its heyday under Patr. Michael I Rabo (1166–99), who had been its abbot before his election as patr. The monastery, which became the regular venue for synods under Michael  I, suffered serious damage by fire in 1183. Michael I was succeeded as patr. by another abbot of Dayro d-Mor Barṣawmo, Rabban Ṣaliba, who as patr. took the name Athanasios (1199–1207), while his rival Michael II the Younger, a nephew of Michael I, had also been educated in the monastery. Patriarchs begin to reside less frequently at Dayro d-Mor Barṣawmo in the following period. Ignatius III Dawid (1222–52), although originally a monk of the monastery, spent much of his patriarchate in Armenian and Frankish territory at Qalʿa Rumoyto (Hromklay, Rum Kale) and Antioch. In the schism following his death Dionysios ʿAngur (1252–61) took up residence in the monastery and was joined there for a time by Bar ʿEbroyo, who was to revisit the monastery as maphrian on at least two occasions. Patr. Ignatius IV Yeshuʿ (1264–83) had to engage in a long dispute over the control of the monastery with its abbot Yaʿqub and his influential brother Shemʿun of Qalʿa Rumoyto. His successor Philoxenos Nemrod (1283–92), a nephew of Shemʿun and Yaʿqub, seems normally to have resided in Dayro d-Mor Barṣawmo, which was badly damaged by an earthquake in 1284/5, and it was there that Barṣawmo Ṣafī, the younger brother of Bar ʿEbroyo, was consecrated maphrian in 1288. The monastery seems to have been deserted not long after the murder in 1293 of Constantine, the Melitenian patriarchal claimant in the three-way schism that followed the death of Philoxenos, and, after the extinction also of the Cilician line of patriarchs, was replaced by Dayr al-Zaʿfarān near Mardin as the normal residence of Syr. Orth. Patriarchs.

The 15th cent. saw a revival of Syr. Orth. activities in the area just to the east of Dayro d-Mor Barṣawmo, centred around the town of Gargar (modern Gerger) and the Monastery of Mor Abḥai. Dayro d-Mor Barṣawmo, too, was reoccupied at that time, as is indicated by a number of manuscripts dated between 1463 and 1675 that either mention or were copied in Dayro d-Mor Barṣawmo. There has been yet another revival of Syr. Orth. communities in the area in recent years, leading to the appointment of a metropolitan for Adıyaman (former Ḥisn Manṣūr) in 2006.

Another Syr. Orth. monastery dedicated to Mor Barṣawmo was the ‘little monastery’ (dayrunitho) of Mor Barṣawmo near Kfartuto to the southwest of Mardin, which is attested in 12th–13th cent. and was situated between the villages of Bagdashiyya (modern Bektaş) and Ḥashray (modern Dikmen) (Honigmann, 44–5; and colophons of mss. Vat. Syr. 147 and Yale, Syriac 10).