The Holy Church of the Virgin Mary (Ιερός Ναός της Παναγίας) is one of the five large churches in the the town of Karpenisi. The Virgin Mary Church was the cathedral during the Turkish occupation. In July 1821 all churches were destroyed and/or burned down.

After the burning of the churches and the whole town of Karpenisi by the Turks in 1821, the people began to settle down again. Their primary goal was to rebuild their churches and school. Each parish was interested in its own hurch and was doing an enviable activity. The present Holy Church of the Virgin Mary was built in 1910 and it is the fourth time that the church has been built on the same site.