The first fortifications at Rhodes were built in the late 5^th century BC, at the time the town was founded. Since then many centuries have elapsed, during which the defences have been extended, remodelled, destroyed, repaired and reinforced, all contributing to the castle’s present-day appearance. It owes much of its present form to the Knights of St. John, who occupied the island in the early 14^th century and stayed there until it fell to the Ottomans in 1522. The castle’s Byzantine phases intervened between the fortifications of ancient times and those of the Knight’s era. The first of these, dating to the late 7th century, is associated with the Arab invasion of the Aegean and systematic raids against the islands. The second, in the late 11^th and mid 12^th century, is linked to Rhode’s emergence as a major Venetian trading station, following permission granted by Emperor Alexius I Comnenus . The walls were then extended southward and gradually reinforced, so that the Hospitallers found themselves up against considerable fortifications during the siege of Rhodes in the early 14^th century. In this phase the walled city was divided into three areas: the citadel, the inner castle (Chollacium), and the Chora or town proper (Burgus).

The arrival of the Knights heralded an era of prosperity and intense building activity for Rhodes. Many Grand Masters, such as Hélion de Villeneuve (1319-1346), Antoni di Fluvià (1421-1437), Jean Bonpart de Lastic (1437 -1454) and Jacques de Milly (1454-1461), carried out projects to repair, reinforce and extend the city walls until they acquired their present length in the mid-15^th century. They are about 3.5 km long and enclose an area of ​​350 hectares. Byzantine sections have survived at certain points in the ramparts, consisting of earthworks and a ditch 20-60 metres wide. Twenty-one strong towers and eight bastions reinforced the walls, in line with the demands made by the introduction of gunpowder weapons, while numerous gates enabled free movement and communication. The castle’s main thoroughfare was the paved Street of Knights, 200m long and 6m wide. It began at the Palace of the Grand Magister and ended at Our Lady of the Castle, a Byzantine church modified by the Knights. The street was lined on either side with the most important buildings in the castle - the Church of St. John in the Collachium, the Inns of Tongues, the Chapel of the Holy Trinity, the Hospital and residences of officials in the Order.

The fall of Rhodes to the Ottomans under Suleiman the Magnificent in 1522 did not result in significant changes to the appearance of the wall, but was reflected in the castle interior by the building of mosques dedicated to Hamza Bey, Suleiman and others.