The Monastery was founded in the second half of the 14th century, a period when the spiritual/ intellectual development of the Byzantines had reached its height, but also a time when a variety of conflicts in the political and ecclesiastical spheres affected the kingdom. During this time, Stephan Dousan led the Serbs to conquer a significant area in Macedonia, while the Ottomans crossed into the European continent for the first time, gaining European land through the conquest of Kallipolis in Thrace.
At a short distance from the site where the present Monastery was built, an earlier monastery (the Monastery of Christ the Saviour) had been operating since the 11th century. However, the ancient tradition of the Monastery links its founding with the name of the Byzantine Emperor Alexis I Comnenos (1081-1117).
According to sources, and primarily the ancient records in the archives of the Monastery, the original founders of the present day Monastery were two important Byzantine military officers from Konstantinople who were militarily active in Macedonia during this period: The brothers Alexis and Ioannis Comnenos, who held the military titles of Commander-in-Chief and Prime Minister, respectively. Their military successes and their relationship through marriage with the Emperor Ioannis V Palaiologos entitled them to vast landholdings in eastern Macedonia (i.e. Chrysoupolis, Anaktoropolis, Thasos, and Christoupolis), a portion of which they later donated to the Monastery. The exact time of the founding of the Monastery is not known. However, it appears likely that the initial construction may have started in the year 1357, and the official founding probably took place between the months of April and August of that year. At the same time (April 1357), the Emperor Ioannis V Palaiologos and the Patriarch Callistos I announced (in an imperial chrysobull and an eccleastical sigilli, respectively) the awarding of the Cell of Ravdouchos (an existing monastery) in Karyes to the two brothers by Theodora I. This Cell was incorporated into the Monastery a short time later, after its official founding. The Monastery appears in surviving ecclesiastical documents the following year (1357), while the Cathedral was opened in 1362/3 by the Patriarch Callisto I, who declared it to be the ecumenical seat; in 1367, the church was characterized as a basilica. The same Patriarch also issued a sigilli relating to the operation of the monastery. Although the document has unfortunately been lost, it is known to have provided guidelines relating to the independence and communal standards of the monks living in the Monastery, and also for their spiritual well-being.
Several years later, between March 1368 and February 1369, Alexis I died, most likely defending the island of Thasos from the Ottomans. The responsibilities as founder of the Monastery were taken over by Alexis' brother Ioannis and the latter's wife Anna Asanina Kodostefanina, as is verified by the documents from this period, mainly from evidence in the provisions in the Will of Ioannis from August 1384.
The unstable political situation and the military successes of the Ottomans led Ioannis to ask the Venetian leader Andrea Kodarini to grant him Venetian citizenship. His request was granted in January 1374, but he managed to avoid ever fleeing to Venice. He remained in Macedonia, continuing to defend his Byzantine properties, such as those in Marmarolimena, Thasos, where he built a tower and wall, and also continuing his economical support of the Monastery. He remained active at least until the end of 1834, when he retired to the Monastery, where he spent the last years of his life.
According to the Monastery tradition, Ioannis became a monk, adopting the monastic name Ioannikios. A memorial to his residence and death in the Monastery around 1836/7 is the 'Tomb of the Founders', which can be found today on the northern side of Litis, inside the cathedral. The tomb is covered with a pseudo-sarcophagus dating to the 14th century, a part of which has been saved.
