The first available information about the Church of Metsovo points to the fact that, in the 14th century, it was part of the Metropolis of Ioannina. Furthermore, there are accounts of the existence of monasteries during the same period in the area as well as in the greater region of the central Pindos. The administrative inclusion of Metsovo in the Ottoman Sanjak of Trikala in the mid-15th century would require corresponding changes in the ecclesiastic administration, but this is not attested before the mid-17th century, when Metsovo was under the Metropolis of Stagoi.
According to Aravantinos, in the 16th century the Patriarchate of Constantinople transferred the exarchate supervising the Vlach villages in the area to the hegoumenos of the monastery of Voutsa. This testimony is evidence of the establishment of a distinct ecclesiastic Exarchate of Metsovo at the time, a development connected with the granting of privileges to Metsovo and the surrounding area. From then until 1924, Metsovo and six neighboring settlements constituted an autonomous church region, supervised directly by the Patriarchate of Constantinople. In 1924, the patriarchal Exarchate of Metsovo was briefly turned into a Metropolis, in order to find posts for high-ranking clergymen from Asia Minor that had lost their sees in the aftermath of the population exchange between Greece and Turkey. In 1929, the Metropolis was abolished without reinstating the exarchate status, and the area of the former Exarchate of Metsovo came under the Metropolis of Grevena until 1932, when Metsovo, Anilio, Votonosi and Derventista were separated and annexed to the Metropolis of Ioannina.