Located on this site since 1647, the cathedral has twice been destroyed by fire throughout the centuries.
A previous iteration of the church was destroyed during the Siege of Quebec in 1759. It was rebuilt from plans by Gaspard-Joseph Chaussegros de Léry draughted in 1743. The belltower, however, was designed by Jean Baillairgé, who also oversaw construction. The interior was designed by Jean Baillairgé and his son François from 1786–1822. In 1843, François' son, Thomas, suggested a reconstruction of the façade to resemble the church of Sainte-Geneviève in Paris, resulting in the finest Neo-classic façade in Québec. The cathedral was richly decorated with impressive works of art: baldaquin, canopy, episcopal throne dais, stained glass windows, paintings, and chancel lamp (a gift of Louis XIV).
In 1922 the church was again gutted by fire, and restored by architects Maxime Roisin and Raoul Chenevert. Raoul Chenevert added a presbytery beside the Cathedral in 1931-32 
In 2014 the cathedral celebrated its 350th anniversary. As part of the celebrations, a holy door was constructed—the first outside Europe and only the seventh in the world. The holy door was opened on December 8, 2013 and is to remain open for a year, after which it will be sealed until 2025.