The Chora Church was originally built as part of a monastery complex outside the walls of Constantinople, to the south of the Golden Horn. Literally translated, the church's full name was the Church of the Holy Saviour in the Country: although "The Church of the Holy Redeemer in the Fields" would be a more natural rendering of the name in English. (Greek ἡ Ἐκκλησία του Ἅγιου Σωτῆρος ἐν τῃ Χώρᾳ, hē Ekklēsia tou Hagiou Sōtēros en tēi Chōrai). The last part of that name, Chora, referring to its location originally outside of the walls, became the shortened name of the church. The original church on this site was built in the early 5th century, and stood outside of the 4th century walls of Constantine the Great. However, when Theodosius II built his formidable land walls in 413–414, the church became incorporated within the city's defences, but retained the name Chora. The name must have carried symbolic meaning, as the mosaics in the narthex describe Christ as the Land of the Living (ἡ Χώρα των ζώντων, hē Chōra tōn zōntōn) and Mary, the Mother of Jesus, as the Container of the Uncontainable (ἡ Χώρα του Ἀχωρήτου, hē Chōra tou Achōrētou).
The majority of the fabric of the current building dates from 1077–1081, when Maria Dukaina, the mother-in-law of Alexius I Comnenus, rebuilt the Chora Church as an inscribed cross or quincunx: a popular architectural style of the time. Early in the 12th century, the church suffered a partial collapse, perhaps due to an earthquake. The church was rebuilt by Isaac Comnenus, Alexius's third son. However, it was only after the third phase of building, two centuries after, that the church as it stands today was completed. The powerful Byzantine statesman Theodore Metochites endowed the church with much of its fine mosaics and frescos. Theodore's impressive decoration of the interior was carried out between 1315 and 1321. The mosaic-work is the finest example of the Palaeologian Renaissance. The artists remain unknown. In 1328, Theodore was sent into exile by the usurper Andronicus III Palaeologus. However, he was allowed to return to the city two years later, and lived out the last two years of his life as a monk in his Chora Church.
During the last siege of Constantinople in 1453, the Icon of the Theotokos Hodegetria, considered the protector of the City, was brought to Chora in order to assist the defenders against the assault of the Ottomans.
Around fifty years after the fall of the city to the Ottomans, Atık Ali Paşa, the Grand Vizier of Sultan Bayezid II, ordered the Chora Church to be converted into a mosque — Kariye Camii. Due to the prohibition against iconic images in Islam, the mosaics and frescoes were covered behind a layer of plaster. This and frequent earthquakes in the region have taken their toll on the artwork.
In 1948, Thomas Whittemore and Paul A. Underwood, from the Byzantine Institute of America and the Dumbarton Oaks Center for Byzantine Studies, sponsored a programme of restoration. From that time on, the building ceased to be a functioning mosque. In 1958, it was opened to the public as a museum — Kariye Müzesi.