Archaeological remains testify to the use of the area as early as the 5th and 6th centuries. The establishment of the fortress is placed in the 12th or 13th century, however, there is no evidence in written sources to confirm this dating. In the 12th century, after the loss of the Byzantine possessions in Italy in 1071, Corfu became a border region of the Byzantine Empire. The island was under constant threat from the Normans, the new rulers of the southern Italian area. The construction of Aggelokastro has been associated with Emperor Manuel I Komnenos, who recaptured the island from the Normans in 1149. According to another view, the castle was built after 1214, during the period when the island belonged to the independent state of Epirus, more widely known today as the Despotate of Epirus. In 1259, Corfu was granted as a dowry to King Manfred of Sicily upon his marriage to Helena, the daughter of Michael II Komnenos Doukas, despot of Epirus. In 1267, the Angevin rulers of Naples occupied the island, and five years later Aggelokastro came into their hands after the Italian Giordano di San Felice took possession of it. The first written mention of the castle appears in the castle handover report, where it is referred to as Castrum Sancti Angeli.

In 1386, Aggelokastro, along with the rest of Corfu, passed to the Venetians. While it remained in use throughout Venetian rule due to its strategic importance for the island’s defence, its significance gradually declined with the development of Corfu’s Old and New Fortresses.

Throughout the Venetian period, Aggelokastro played a crucial role during the Ottoman raids of 1537, 1571 and 1716, repelling attacks and offering refuge to the inhabitants of the wider region. Venetian historian Marco Guazzo records four failed Ottoman attempts to capture it. After the French occupation of Corfu in 1797, the castle probably served as an observatory, while during the early part of British rule (1814–1864) it fell into disuse.