The importance of Zouk Mikael rose in 1305 AD, during the Mameluke and Crusader eras, as Zouk was the center of Keserwan's coastal guard against the Crusader's attacks. It was also known as one of the rebellious villages that resisted tyranny and Mameluke occupation.
When several attempts to occupy Keserwan occurred, its citizens - mostly Maronites - stood together in order to preserve their independence from the Mameluke state.
In 1304, after a 3-year siege, the governor of Damascus succeeded in conquering Keserwan from the north, where he destroyed churches and burned down villages, including Zouk. The establishment of Souks reflected negatively on the Maronites' political, military, and economic force, as Zouk suffered from a great deal of theft and murder.
With the Ottoman occupation in 1541, Zouk was established as the first main headquarters of the State of Damascus, received several families, and witnessed important demographic and political changes. When the Turks left the village, the Al-Khazen family bought all their properties.