Syria had been under Roman rule for seven centuries prior to the Arab Muslim conquest and had been invaded by the Sassanid Persians on a number of occasions during the 3rd, 6th and 7th centuries; it had also been subject to raids by the Sassanids' Arab allies, the Lakhmids.

During the Roman period, beginning after the fall of Jerusalem in the year 70, the entire region (Judea, Samaria, and the Galilee) was renamed Palaestina. During the last of the Roman-Persian Wars, beginning in 603, the Persians under Khosrau II had succeeded in occupying Syria, Palestine and Egypt for over a decade before being forced by the victories of Heraclius to conclude the peace of 628. Thus, on the eve of the Muslim conquests the Romans (or Byzantines as modern Western historians conventionally refer to Romans of this period) were still in the process of rebuilding their authority in these territories, which in some areas had been lost to them for almost twenty years.

The Byzantine (Roman) Emperor Heraclius, after re-capturing Syria from the Sassanians, set up new defense lines from Gaza to the south end of the Dead Sea. These lines were only designed to protect communications from bandits, and the bulk of the Byzantine defenses were concentrated in Northern Syria facing the traditional foes, the Sassanid Persians. The drawback of this defense line was that it enabled the Muslims, advancing from the desert in the south, to reach as far north as Gaza before meeting regular Byzantine troops.