Throughout the Islamic era and until the modern day, the Arabic name of the city was pronounced in a number of different ways by the inhabitants of the region as Maṣyaf, Maṣyat or Maṣyad.

Roman and Byzantine historians mentioned a city named "Marsyas" that governed the al-Ghab and Beqaa plains to the north and south of the site, respectively.

In the autumn of 999, Basil II, the Byzantine emperor, destroyed the fortifications at Masyaf as part of his campaign to gain control of Antioch and its environs from the Muslims.

[5] The area would later come under Seljuk rule, but in 1099, the Crusaders attempted to wrest control of Masyaf (and the more strategically important Rafania) following their capture of Tripoli.

The fortress was being defended by a Banu Munqidh mamluk (slave warrior) named Sunqur, who the Ismaili force managed to ambush and kill.

Consequently, the surviving Ismaili leadership decided that establishing bases in Syria's cities and thus relying on the goodwill of various umara (princes) was untenable.

Together with other fortresses acquired at around the same time, including al-Kahf, Khawabi, al-Qadmus and al-Rusafa, the Ismailis were able to carve an autonomous territory for themselves amid hostile Crusader states and local Muslim dynasties nominally affiliated with the Abbasid Caliphate.

He arranged a truce with Sinan mediated by the Ayyubid emir of Hama, Shihab al-Din Mahmud al-Harimi, Saladin's uncle.

Mubarak was later imprisoned in Cairo by Baibars and Najm ad-Din was briefly restored as emir before Masyaf was fully incorporated into the sultanate in 1270.

[6] Towards the end of the century, Masyaf became a major stopping point on the Mamluk postal route and was controlled by a commander who answered directly to the sultan due to its strategic role as a frontier fortress.

[14] In 1320, the historian and Ayyubid emir of Hama, Abu'l Fida, noted that Masyaf was a "center of the Ismailian Doctrine" and that it was "beautiful" with gardens and a spring from which flowed a small stream.

[15] According to Ibn Battuta, who passed by the town in 1355, Masyaf was the center of a district belonging to the province of Tripoli and containing the fortress villages of al-Rusafa, al-Kahf, al-Qadmus, al-Ulayqa and al-Maniqa.

In the mid-15th century, under Sultan Barsbay, a road was built that connected Masyaf with Tripoli, but the postal route no longer passed through the town.

Masyaf became a part of the liwa (district) of Homs, and along with the other Ismaili fortresses in its vicinity (qala' al-da'wa), was responsible for paying a special tax.

According to the Sufi traveler Abd al-Ghani al-Nabulsi, the emir of Masyaf in the early 1690s was a descendant of the Arab Tanukh tribe named Sulayman.

[14][17] About 300 of the town's Ismaili inhabitants were also killed,[14] while many others, including the da'i (religious chief) of Masyaf, fled for Homs, Hama and other areas in central Syria, settling in those places temporarily.

[20] In the 1960s, Masyaf's Ismaili community largely identified with the Nasserist movement, in contrast to the Alawites who dominated the surrounding villages who were mostly associated with the Baathists.

[25] In the Syrian Civil War after 2015, an alleged missile production facility in Masyaf and a base near the town, thought to be used by Iranian forces and militias, became repeatedly targets of airstrikes attributed to Israel.

[26] On 8 September 2024, Israel launched a series of airstrikes as well as a ground raid by the Shaldag unit, targeting an underground precision missile factory reportedly built by Iran.

[5] Nearby villages include al-Rusafa to the southeast, al-Bayda to the south, al-Suwaydah to the southwest, Rabu to the west, Biqraqa to the northwest, Hurayf and Hayalin to the north, Zaynah to the northeast and al-Shiha to the east.