The Great Mosque of Hama stands on a site of continuous religious use stretching back to the Roman period, when a temple to Jupiter occupied the same ground. The Byzantines converted the temple into a cathedral dedicated to Saint John the Baptist; after the Arab conquest of 637 AD, the cathedral was shared briefly between Christians and Muslims before being converted into a mosque under the Umayyad caliphs — following the same sequence as the more famous Great Mosque of Damascus, built on an identical pattern of Roman temple to Byzantine church to Islamic mosque. Elements of the Roman colonnade and Byzantine stonework are still visible in the mosque's courtyard walls and the base of the minaret.
The mosque was substantially rebuilt in the Ayyubid period and again after the Mongol invasions of the 13th century, giving it a layered architectural history. Its courtyard is one of the more expansive in Hama's old city, and the interior — when it was open to respectful visitors — displayed the characteristic features of Syrian mosque architecture: an ablution fountain at the centre of the courtyard, a deep prayer hall oriented toward Mecca, and an elegantly restrained decoration that contrasts with the elaborate ornamentation of Ottoman mosques. The building occupies the oldest religious ground in the city.