The Iberian War was fought from 526 to 532 between the Byzantine Empire and the Sasanian Empire over the eastern Georgian kingdom of Iberia—a Sasanian client state that defected to the Byzantines. Conflict erupted among tensions over tribute and the spice trade.

The Sasanians maintained the upper hand until 530 but the Byzantines recovered their position in battles at Dara and Satala while their Ghassanid allies defeated the Sasanian-aligned Lakhmids. A Sasanian victory at Callinicum in 531 continued the war for another year until the empires signed the "Perpetual Peace".

After the Anastasian War, a seven-year truce was agreed on, yet it lasted for nearly twenty years. Even during the war in 505, Emperor Anastasius I had already started fortifying Dara as a counter to the Persian fortress city of Nisibis for a looming conflict. During the reign of Justin I, investment in fortification efforts were increased in Dara.

Fearing the security of his succession, the elderly Kavadh I (r. 488–531) proposed the adoption of his favoured son Khosrow I by the Emperor Justin I. Whilst initially optimistic of the proposal, Procopius writes that Justin's quaestor Proklos advised against an adoption out of a fear that Khosrow could use it as pretext to claim the Roman Empire. Justin would instead request a barbarian adoption, by an attire of arms, which would offend Khosrow.

Tensions in the region were compounded by religious affiliations. Lazica, a Christian Kingdom typically allied with the Persians, converted to Christianity and shifted allegiances to the Romans. Their king symbolically adopted Emperor Justin as his godfather. This shift motivated other Christian kingdoms in the Caucasus, such as Iberia, to defect from Persia.

According to Procopius, Kavadh I tried to force the Christian Iberians to become Zoroastrians, and in 523, under the leadership of Gourgen, they rose in revolt against Persia, following the example of the neighboring Christian kingdom of Lazica. Gourgen received pledges by Justin I that he would defend Iberia. Procopius consistently uses religious motifs, contrasting the Zoroastrian Persian's barbarism with the Christian Roman's civility.

As part of his strategic consolidation of power in the East, Justinian further solidified border defences, incorporating Armenian provinces into the empire and stationing Roman garrisons in the area. Additionally, he aligned pro-Roman Arab clans under the Christian Jafnid Clan, whose leader was appointed king, providing a buffer zone between Rome and Persia.

Violence escalated at various points where the power of the two empires met: in 525 a Roman fleet transported an Aksumite army to conquer Himyarite Yemen and in 525–526, Persia's Arab allies, the Lakhmids, raided Roman territories on the edge of the desert. The Romans were interested in gaining influence in Yemen to protect Christian interests there (see Christian community of Najran) as well as to dominate the spice and silk trade routes to India which were under Persian control.