With the foundation of Constantinople as the Roman capital in the East, a synthesis of Roman civic thought, Greek philosophy and the Eastern Christian religion was achieved. Salamina, resuming its role as capital, was rebuilt by Constantius XI (337-361 AD) and renamed Constantia.

Since its adoption by Constantine as an official religion, Christianity spread rapidly throughout the empire. In 431 AD a dispute arose between the bishops of Cyprus and the patriarch of Antioch, who claimed ecclesiastical jurisdiction on the island. The independence of the Church of Cyprus was finally confirmed by the Byzantine emperor Zeno in 488 AD, after Anthemios, bishop of Constance, presented Zeno with the relics of Santa Barbara, whose position was revealed to him in a dream.

For the next hundred years Cyprus remained quiet and undisturbed. But from Arabia a new and powerful power was gathering its strength. Islam spread like wildfire across Syria, Palestine and Egypt, and in 649 AD an Arab fleet of 1700 ships appeared off the coast of Salamis. The city was sacked and other cities were sacked and burned. From the 7th to the 10th century AD the island was repeatedly subject to Arab raids and, at times, the tribute was paid to the Caliphate and the taxes to Constantinople. During this period many cities were abandoned and many ancient and early Christian buildings were destroyed. The inhabitants of Salamina / Costanza finally moved and settled in Arsinoe, which later became Famagusta.

The devastation did not end until the emperor Niceforo Foca finally conquered the rise, leading the Muslim invaders from Cyprus and other parts of his kingdom. To protect the island from further incursions, the 11th century mountain castles of Saint Hilarion, Buffavento and Kantara were built. In addition, new fortifications were built for Kyrenia and Nicosia.

During this period there was a division between the Orthodox and Latin churches. The head of the Orthodox church had warned his people against the errors of the Latin church and was promptly excommunicated for this.

After a difficult truce with the Muslim leader Saladin, raids from the kingdom of Jerusalem on Muslim pilgrims to Mecca in 1181 began to increase tensions in the region. Events began to lose control when the Christian king died of leprosy in March 1185, causing the Kingdom leadership to fragment. After the death of the young heir, the ex-brother-in-law of the king, Guy of Lusignano, was crowned king in 1186.

This caused dissension among the Crusaders. Guy was hated by powerful rivals for the crown and, when he arrived at the throne, he was unable to exercise any real control over his kingdom. At that time the great Saladin had united Muslim nations and embarked on a jihad to retrieve Jerusalem. The tide had changed, and Saladin eventually delivered his attack with united forces and with a spirit equal to that which had fired the Christians of the first crusade, since Jerusalem was also a holy place for Muslims.

In 1187, Guy di Lusignano's army was completely defeated and, after a fifteen-day siege, Jerusalem was taken. Only the city of Tire remained of the kingdom itself, together with the principalities of Antioch and Tripoli in the North.

The fall of Jerusalem shocked Christianity and the European powers, which organized the Third Crusade. The Germans went by land, but the French, led by Philip II, and the British, led by Richard the Lionheart, decided to travel by sea to Acre. On the way, Richard 's fleet was dispersed by a storm; several ships were wrecked off the coast of Cyprus and the one in which Richard 's fiancée was sailing took refuge in the port of Limassol. The year was 1191 and the self-proclaimed emperor Isaac Commenos ruled Cyprus. He made the fatal mistake of arresting Richard 's shipwrecked men and of abusing his fiancée Berengaria. When Richard arrived a few days later, he landed in force and grabbed Limassol. Isaac capitulated and swore allegiance to Richard, but immediately broke his oath and fled to Kantara. Eventually he was captured at Cape Andreas on the Karpaz peninsula by Guy of Lusignano, who had arrived in Cyprus to join Richard.

A year later Richard sold the island to the Knights Templar for 100,000 Byzants.

The dominion of the Templars in Cyprus was marked by great severity and they quickly faced the hatred of the Cypriots for their harsh exactions. In the end, desperate for their treatment and seeing that the Templars were few, the islanders decided to attempt a general massacre of the knights on Easter day of 1192. The Templars became aware of the plot and took refuge in their fortress in Nicosia, as they were too few to meet the insurgents outdoors. They offered to leave the island if their lives were spared, but since this offer was rejected, they decided to fight rather than be submissive.

Attacking on the streets at dawn, they surprised and massacred a large number of Cypriots, sparing neither women nor children. The rebellion was crushed, but the Templars felt unable to hold Cyprus by force and therefore asked Richard to take back their purchase. He accepted and the Templars withdrew to Syria, while retaining some of their possessions in Cyprus.

Upon the death of his wife Sybilla, Guy of Lusignano's claim to the crown of Jerusalem weakened and was therefore deposed by the barons. To compensate for his loss, Richard offered him the island of Cyprus, and thus began the Lusignano dynasty, which lasted for 300 years.