The church of Panagia Portaitissa constitutes the religious centre of the island and the most renowned and visited spot of worship. It started being built in 1762 by Saint Anthimos from Kefalonia, who, despite the fact that he was blind, had previously built the monasteries of Zoodochos Pigi at Sikinos and of Saint George in Kastellorizo. The construction of the church lasted for nine years and, during those years, a plethora of miracles are said to have happened according to religious tradition.
The church is dedicated to Panagia Portaitissa of the Holy Monastery of Iviron. A copy of the icon of Panagia Portaitissa of this monastery at Mount Athos was brought to Astypalaia by Saint Anthimos.
On August 15th, when Panagia Portaitissa is celebrated, a big festival with violins and lutes is held to honour Her. Near the monastery operates the ecclesiastic museum of Astypalaia where rare relics of exquisite art are on display.