At the point where the Metropolis of Ioannina is located today (1, Metropolis street), there was a Monastery dedicated to Saint Athanasios the Great. After the failed movement of Dionysios the Philosopher (Dionysios Skylosophos), in 1611, and the expulsion of Christians from the castle of Ioannina, the church of Saint Athanasios replaced the cathedral of Pantocrator inside the castle and became the third Cathedral of the city. However, in August 1820 the temple was destroyed by a large fire during the siege of Ali Pasha.

During the presidency of the Metropolitan of Ioannina Ioakeim, in 1832, and at the expense of the brothers Zosimades and other benefactors, a bigger church was rebuilt from the ground up. The frescoes are the work of the Kapesovite hagiographers Theodosios and his son Konstantinos and date back, according to an inscription, to 1835 while the ornate wood-carved iconostasis is "baroque", made of walnut wood, and is the work of four wood carvers from Gorgopotamos, Konitsa, Anastasios Skalistis and his sons Konstantinos, Giannis and Dimitrios.