Constructed by the master carpenter of the Glover Residence, Koyama Hidenoshin, it was originally a small wooden church with three aisles and three octagonal towers.

The church was officially a chapel for the French foreign community in Japan per the Treaty of Amity and Commerce between France and Japan, as Christianity was still officially outlawed by the Tokugawa shogunate.The dedication ceremony was attended by foreign residents, as well as the captains of French, Russian, British, and Dutch ships anchored in Nagasaki Port, each accompanied by several Catholic sailors.

"[4] Petitjean discovered that these people were from the nearby village of Urakami and were Kakure Kirishitans, descendants of early Japanese Christians who went into hiding after the Shimabara Rebellion in the 1630s.

[5] During World War II, the cathedral was damaged by the atomic bomb on August 9, 1945, but avoided collapse and burning due to being relatively far from the hypocenter.

[5] It was the first Western-style building in Japan to be given this honor and remained the only one until 2009 when the neo-Baroque Akasaka Palace was designated a National Treasure.

[8] On June 30, 2018 Ōura Cathedral, along with 11 other sites linked to Catholic persecution in Japan, was added to the UNESCO World Heritage List.