Al-Shaykh Maskin has been identified as the ancient Roman-era site of "Neapolis." By the 4th-century, Neapolis had grown to become a city. A church was consecrated there in 517 during Byzantine rule. In his short article in the Catholic Encyclopedia of 1911, Siméon Vailhé reported that many authorities at that time thought that Al-Shaykh Maskin might be the site of the ancient city and bishopric of Maximianopolis in Arabia, whose identification with nearby Shaqqa is today accepted.
The Ottoman Empire annexed the region in 1516. During this period al-Shaykh Maskin was settled by local Bedouin tribesmen and benefited from the annual hajjpilgrimage to Mecca by supplying pilgrim caravans with camels for transportation. In 1596 al-Shaykh Maskin appeared in the Ottoman tax registers as Samsakin and was part of the nahiya of Bani Malik al-Asraf in the Qada Hawran. It had an entirely Muslim population consisting of 56 households and 17 bachelors. A fixed tax rate of 40% was paid on wheat, barley, summer crops, goats and/or beehives; a total of 17,250 akçe. 1/3 of the revenue went to a waqf. In the 1850s al-Shaykh Maskin contained about 100 houses and all of its inhabitants were Muslims. The town's chief commodity during the 19th-century was grain, which it exported locally. Timber and cloth were the principal imports. Goods traffic was concentrated in the town's railway station which also served all the villages between Sheikh Maskin and the Lajat region. In the It grew considerably between 1891 and 1900. The town hosted the administrative offices of Hauran's local government in the latter half of this century. The population was "exclusively Muslim" according to John Murray. Its sheikh was Ahmed al-Hariri also known as Ahmed al-Turk who served as the Sheikh Mushaikh al-Hauran. His tribe claimed descent from the family of the Islamic prophetMuhammad and were thus known as sharifs. In the wake of the 1860 confrontations between the region's Druze and Christians, Sheikh Ahmed al-Turk led a force of 200 tribesmen to Daraa, rescuing the over 500 Christians in that town from an impending attack by the Druze of the Lejah who his forces successfully routed. He subsequently notified all the tribal chieftains of the area to spare the Christians living in the towns under his authority, to which all the tribes conformed. In 1895 al-Shaykh Maskin became a refuge for the residents of some dozen villages destroyed by Druze fighters in response to an Ottoman decree ordering the conscription of Druze men into the Ottoman army. Ottoman troops mobilized at al-Shaykh Maskin in preparation of the conscription expedition against the Druze which was launched from the town on 15 October. Vital Cuinet wrote in 1896 that al-Shaykh Maskin's population of 800 included 400 Muslims and 400 Greek Orthodox, while Gottlieb Schumacher described it in 1897 as "large and prosperous".
On 14 November 2015, Syrian troops advance in the town Sheikh Meskin and seizing some parts of it. On 20 November 2015, the Free Syrian Army launched a large-scale counter-assault inside the city in order to force the Syrian Army to exit the west district. However, the Syrian Army struck the FSA which forced it to retreat towards the east district. Recently, the Syrian Army has concentrated on the city after they conceded it to the Free Syrian Army last year. Over the course of a week, the Syrian Army has recovered several sites around the city, including the Water Pump Factory, Battalion 82 Engineering Base, and Al-Dilli. On 26 November 2015, it was reported that clashes were taking place between the army and the rebels in the vicinity of the city, where the army was trying to advance towards the city, while the rebels were trying to regain control of the areas controlled by the army on the outskirts of the city weeks ago. On 30 December 2015, it was reported that the advancing Syrian government troops and militiamen had reached the main square. On 26 January 2016, the Syrian government announced it had "established full control" over the town "as a result of a wide-scale military operation conducted by the army, in cooperation with the supporting units".
