Several Byzantine-era ruins attest to its regional importance, though the historian Elizabeth Kay Fowden asserts "little evidence remains to help reknit the town's history".

[5] An undated inscription credits the locals' patronage of the town's fortifications and honors St. Sergius, a popular saint amongst the Christian inhabitants of the Syrian steppe.

Caliph al-Mahdi, Abdallah's cousin and brother-in-law, stayed in Salamiyah and admired his house there on his way to Jerusalem in 779–780 and appointed him governor of the Jazira.

[3] Around the early 9th century, Salamiyah became home to the great-grandson of Ja'far al-Sadiq, Abdallah, who concealed his identity and pretended to be a regular member and merchant of the Banu Hashim (the clan to which both the Abbasids and Alids belonged).

The Qarmatians razed Salamiyah in 903, massacring its inhabitants, though Abdallah al-Mahdi had left the city the year before and went on to establish the Fatimid Caliphate.

The town, which during this period was unfortified, remained administratively attached to Homs and was on several occasions used as a marshaling point by Muslim armies campaigning against the Crusader states and Byzantine Empire.

The Seljuk atabeg and founder of the Zengid dynasty, Imad al-Din Zengi, mobilized his troops in Salamiyah for his campaign against the Byzantines at Shaizar in 1137–1138.

[8] The founder and first sultan of the Ayyubid dynasty, Saladin, took over Homs, Hama and Salamiyah from the Zengid emir Fakhr al-Din Za'afarani in 1174–1175.

Homs and Salamiyah were granted to his cousin Muhammad ibn Shirkuh and remained in the latter's family until the death of its last Ayyubid emir al-Ashraf Musa in 1163.

[10] It was a large ruin which, in the 16th–18th centuries, served as a stronghold for the Al Hayar (or Abu Risha) emirs of the Mawali tribe, who were recognized by the Ottoman authorities as the commanders of the Bedouin of the Syrian steppe.

[12] In 1623, the chief of the Harfush emirs of Baalbek, Yunus al-Harfush, was imprisoned in Salamiyah by a Bedouin ally of Mudlij, Khalil ibn Ajaj, butwas released by the intercession of Fakhr al-Din.

[16] In July 1849, Isma'il ibn Muhammad, the Isma'ili emir of Qadmus in Syria's Jabal Ansariya coastal mountain range, obtained a firman from Sultan Abdülmecid I granting him permission to settle Salamiyah and its environs with his followers.

[20] Thereafter, significant migrations of Isma'ilis from Jabal Ansariya to Salamiyah followed,[21] the new arrivals drawn to the area by higher prospects of prosperity than in the coastal mountains, taxation and conscription exemptions, and the medieval connections with their faith.

The growing number of Isma'ili emigrants began to branch out to the long-abandoned villages in Salamiyah's orbit and recultivated its fertile lands.

[18] In 1884, under Sultan Abdulmejid II, Salamiyah and its environs were made a kaza of Hama and its residents were subject to taxation and conscription.

By the close of the 19th century, Salamiyah, with its 6,000-strong population, was the largest Isma'ili center in the Ottoman Empire, and had a well-developed irrigation network.

[24] The importance of Salamieh diminished following the Syrian Army's securing of the Homs-Hama Motorway on February 1, 2018, during the Northwestern Syria campaign.

During the 2024 Syrian opposition offensive, regime forces withdrew from the city, which was subsequently seized by Hay'at Tahrir al-Sham militants on 5 December 2024.