Palestine was severely affected by the Holy Desert Quake South. Several Christian chroniclers describe a powerful earthquake affecting Palestine and the Jordan Valley, with large numbers of fatalities and the collapse of churches and monasteries. The destruction was reportedly particularly severe in the desert or wilderness surrounding Jerusalem. These accounts are preserved by Paul the Deacon, Theophanes, Anastasius Bibliothecarius, Megas Chronographos, and George Cedrenus. The geographic emphasis of these accounts on Palestine, the Jordan, and especially the wilderness surrounding Jerusalem is consistent with the southern epicentral region proposed for the Holy Desert Quake South.

Jerusalem itself also appears to have suffered destruction. al-Dhahabī describes the earthquake as exceptionally violent in Jerusalem, reporting fatalities and the collapse of the houses of the family and and guests of Shaddad ibn Aws. A later account by Ibn Taghri Birdi similarly states that the earthquake destroyed Jerusalem and that survivors remained outside the city for forty days. Abu l-Fath also describes an extraordinarily powerful earthquake during the reign of Caliph Marwan II (r. 744-750 CE) in which houses collapsed on their inhabitants and survivors remained in the open while the ground continued to shake.

A particularly detailed Jerusalem tradition is preserved by Mujir ad-Din al-'Ulaimi. His account, which describes a succession of shocks followed by the main shock on a cold, rainy night, states that houses throughout Jerusalem had been destroyed. He also preserves traditions concerning unusual movements of the Dome of the Rock during the shaking, including reports that the dome was temporarily displaced sufficiently for the night sky to be visible before it settled back into position. These stories contain legendary elements but nevertheless preserve a tradition of repeated strong shaking and extensive destruction in Jerusalem.

Al-Aqsa Mosque sustained major damage. According to al-Dhahabī, the eastern and western portions of the mosque were damaged in an earthquake. A more detailed tradition preserved by Jamal Ad Din Ahmad states that the earthquake threw down both the eastern and western parts of the mosque. The damage was sufficiently extensive that, during the reign of Caliph al-Mansur (r. 754-775 CE), gold and silver plates covering the mosque's gates were removed and converted into currency to finance reconstruction.