The monastery of Hosios Loukas was founded in the early 10th century AD by the hermit, Venerable Luke of Steiris, whose relics are kept in the monastery to this day. A church dedicated to Saint Barbara, which forms the core of the present-day church, was likely built during his lifetime.

The monastery derived its wealth from the fact that the relics of St. Luke were said to have exuded a sort of perfumed oil which produced healing miracles. Pilgrims were encouraged to sleep by the side of the tomb in order to be healed.

At the heart of the monastery complex lie two interconnected churches: the Katholikon and, on slightly higher ground and adjoining to the northeast, the Theotokos Church. The Katholikon, the main church dedicated to Saint Luke and dating from 1011, represents a type of church that was new at the time. This elongated rectangular structure is a cross-in-square domed church, a style otherwise characteristic of medieval Armenian architecture.
Its plain exterior walls are constructed of brick and ancient stone blocks, the latter possibly transported here from Delphi. The interior contrasts sharply with the rugged exterior; the church is spanned by a fresco-adorned dome with a diameter of nine meters.