The city of Ilānṣurā mentioned in the Akkadian and Northwest Semitic texts of the Mari Tablets (1800–1750 BC) may possibly be Hasankeyf, although other sites have also been proposed.

[6] By the Roman period, the fortified town was known in Latin as Cephe, Cepha or Ciphas, a name that appears to derive from the Syriac word ܟܐܦܐ (kefa or kifo), meaning "rock".

As the eastern and western portions of the Roman Empire split around AD 330, Κιφας (Kiphas) became formalized as the Greek name for this Byzantine bishopric.

The Akkadian and Northwest Semitic texts of the Mari Tablets (1800–1750 BC) refer to Ilānṣurā, an important walled city on a large river.

Following the death of the emperor Julian at the Battle of Samarra, his successor Jovian was forced to surrender to the Persian King Shapur II the eastern provinces of Arzanene, Moxoene, Zabdicene, Corduene and Rehimene.

[11] Recording the situation at the end of the fourth century, the Notitia Dignitatum identifies Cepha as the seat of the commander of the Legio II Parthica.

[20][21] Over the subsequent five centuries, the town was ruled Arab dynasties under the name Hisn Kayfa, first by the Ummayad and Abbasid caliphates and later by semi-autonomous Hamdanid and Marwanid rulers.

The infrastructure, location and significance of the city helped increase trade and made Hisn Kayfa a staging post on the Silk Road.

[26] By 1229/1230, al-Salih's successor, Rukn al-Din Madud, was allied with the Khwarazmshah Jalal ad-Din Mingburnu against the Ayyubid rulers al-Ashraf and al-Kamil.

[28] Troubled by the alliance with Khwarazm, al-Ashraf and al-Kamil resolved to attack Amida, and used as a pretext reports of al-Masʿud's misrule, including his abuse of local women.

al-Ashraf recruited the rulers of Aleppo and Homs to his faction and sent ambassadors to the court of Rum Seljuk sultan 'Alā ad-Dīn Kayqubād to propose an alliance.

[34] The Middle East historian R. Stephen Humphreys speculates that Kaykhusrau was offered control of Amida and Hisn Kayfa in return for joining the alliance.

[34] Although al-Ashraf had assembled a formidable alliance against his brother, he was unable to use this to engage al-Kamil's forces as he was already ill by the time of the negotiations with the Seljuks, and he died on 4 Muharram 635/28 August 1237.

Al-Kamil had bequeathed control of the Jazira to as-Salih Ayyub, who had been emir of Hisn Kayfa, and named his younger brother al-Adil as his heir in Egypt.

[38] Although little remains standing from this prosperous period of the town's history, there is a detailed contemporary first-hand account by the topographer ʿIzz ad-Dīn Ibn Shaddād, whose last visit was in AH 657 (1258/1259).

[39] He lists many buildings in the lower town, including a Dār as-Salṭana (near the bridge), a mosque, three medreses, four hammams, tombs, caravanserais and bazaars.

[39] The German historian of Islamic art Michael Meinecke notes that almost none of the buildings that Ibn Shaddād describes can be identified in present-day Hasankeyf, and attributes that to neglect following the subsequent Mongol invasions and political instability.

[39] In 1255, the great khan Möngke charged his brother Hulagu with leading a massive Mongol army to conquer or destroy the remaining Muslim states in southwestern Asia.

[40] On 23 Rabiʿ II 658/7 April 1260, Mayafaraqin fell to Hulagu's forces, presumably during their retreat towards Ahlat and Tabriz, leaving Mardin and Hisn Kayfa as the only cities outside his control in the Jazira.

[40] Mardin was captured by the end of 1260, but Hisn Kayfa appears to have escaped a concerted assault because it controlled only a minor trade route and could simply be bypassed.

[41] While most of the Diyar Bakr came under direct control of the Mongol governor or Mosul, both Ayyubid Hisn Kayfa and Artukid Mardin were allowed to remain as vassal states.

[41] By AH 665 (1266/1267) the Mamluk Baybars was in power in Egypt, and represented the primary force opposing the Mongols, now led by Hulagu's son Abaqa Khan.

[43] The economy of the region gradually shrank during the 14th and early 15th centuries, according to historian Thomas Alexander Sinclair, but this probably did not cause any population decline in the cities of Mardin or Hisn Kayfa, where building continued uninterrupted.

[46] Soon after, Al-Adil installed Zeyd, a Kurdish chief of the Zraki (or Zirki) tribe previously based at the castle of Boşat (the present-day village of Boyunlu, in Silvan district), as his client ruler at Mayafaraqin.

[48] While Uzun Hassan managed to extend his influence throughout much of the Diyar Bakr and Jazira during the 1450s, the Ayyubid emir of Hasankeyf rebelled in 1460, attempting to take control of Siirt.

Hassan's army of light cavalry was routed by Mehmed II's Ottoman forces, armed with rifles and cannon, at the Battle of Otlukbeli near Erzincan in August 1473.

[52] In his 1614 History of the World, Walter Raleigh places "the Citie of Hasan-Cepha, otherwise Fortis Petra", upstream from the island of Eden, which he believed lay in the Tigris, based on his reading of Andreas Masius's De Paradiso Commentarius.

[63][64] According to the Buğday Association, based in Turkey, Ms. Huriye Küpeli, the prefect of Hasankeyf, the Swiss ambassador to Turkey and representatives of the Swiss led consortium of contractors for the dam project have suggested what they believe to be a suitable nearby spot for moving the historical heritage of Hasankeyf, an operation for which the Turkish Ministry of Culture pledged to provide 30 million euros, however current reports indicate that only eight historical monuments have been moved.

[67] While this listing has created more awareness of the project, it has failed to prompt the Ilısu Consortium to develop alternate plans that are sympathetic to this site of exceptional historical and cultural significance.

In December 2008, following pressure from campaign groups, export credit insurers in Austria, Germany and Switzerland announced suspending their support for the project amid concern about its environmental and cultural impact and gave the Turkish government 180 days to meet standards set by the World Bank.