The Church of St Antony the Great is the oldest church in the Monastery dating back to the time of St Antony, and witnessed many events during its long history. The oldest of the wall paintings date back as early as the 6th century. This church is significant for two reasons: (1) it contains the greatest treasured relics of the blessed founder, St Antony the Great, which rest under the main sanctuary; (2) it contains the most exquisite and uniquely complete wall paintings dating back to the 13th century. Almost eight centuries of dirt and smoke had coloured these exquisite paintings black and made them unrecognisable, until a team of Italian conservators working for the American Research Centre in Egypt, and funded by USAID, undertook the extensive task of cleaning and restoring the wall paintings. This project was completed in 1999, and to celebrate this endeavour, a wonderful book on the Monastery and the wall paintings conservation project was compiled entitled
Monastic Visions.

The wall paintings in this ancient church are unique in that they are unusually complete and cover the entire length and breadth and height of the church. They depict Christ enthroned, the Virgin Mary enthroned, angels and cherubim, the four creatures of the Apocalypse, Old Testament patriarchs, patriarchs of the Alexandrian Church, monastic fathers and equestrian martyrs, and beautiful geometric designs. The painted program is also unique because it provides a dated inscription. Painted in beautiful vibrant colours, the inscription states the paintings were finished in 949 AM (1232-1233 AD). Without doubt, the wall paintings contained in this ancient church are by far one of the greatest monuments of ancient Christian art.

Following the remarkable restoration work, the church was re-consecrated by His Holiness Pope Shenouda III in 2003.

The south-western corner of the Church contains a small chapel dedicated to the Four Living Creatures of the Apocalyse and is believed to date back as early as the 4th century. It is the oldest part of the church where St Antony would gather with his monks for prayer and spiritual contemplation. Some of the wall paintings within this chapel date back to the 6th century.

On the southern wall of the main church is a small door from which there is a passage way leading to the 15th century Church of the Holy Apostles. Within this passage way rests the relics of the monk Yostos (1910-76), a contemporary saint known as ‘the silent monk’, who lived his monastic life within this Monastery. He was known for his strict asceticism, silence and gentleness, and many miracles are attributed to him.