During the Byzantine period (starting 390 CE), the region previously part of the Roman Empire became dominated by Christianity under Byzantine rule.This shift was accelerated by the influx of Christian pilgrims and the construction of churches at biblical sites.^[123] Monks also played a role in converting local pagans by establishing monasteries near their settlements.^[124]

The Jewish community in Palestine faced decline, losing its majority status by the fourth century.^[125] Restrictions on Jews increased, including prohibitions on building new worship places, holding public office, and owning Christian slaves.^[126] The Jewish leadership, including the Nasi office and the Sanhedrin, was dissolved in 425, with the Jewish center in Babylonia rising to prominence thereafter.^[123]

The 5th and 6th centuries saw Samaritan revolts against Byzantine rule, which were suppressed, diminishing Samaritan influence and reinforcing Christian dominance.^[127] Records of Jewish and Samaritan conversions to Christianity during this period are limited and mostly pertain to individuals rather than communities.^[128]

In 611, Khosrow II of Sassanid Persia, aided by Jewish forces, invaded and captured Jerusalem.^[129] The capture included the seizure of the "True Cross". Nehemiah ben Hushiel was appointed governor of Jerusalem. In 628, after a peace treaty with the Byzantines, Kavad II returned Palestine and the True Cross to the Byzantines. This led to a massacre of Jews in Galilee and Jerusalem by Heraclius, who also renewed the ban on Jewish entry into Jerusalem.^[130]