In the spring of 1721, René-Charles de Breslay and Marie-Anselme de Metivier, priests of the Society of Saint Sulpice, arrived at the Acadian settlement of Port-LaJoye and built a small church dedicated to Saint John the Evangelist.

Roughly three years after separation from Nova Scotia and becoming its own colony, a further expansion of the Church on now-renamed Saint John's Island began in 1772, when the first band of about 200 Scottish Catholic immigrants set foot, led by the layman John MacDonald of Glenaladale.

[5] Another group of Scots settled in 1790, led by Angus MacEachern, to join their families who had migrated earlier.

On July 20, 1946, another piece of its territory was split off again, as the Magdalen Islands were transferred to the Diocese of Gaspé.

Although it was closed down by Bernard Donald Macdonald in 1844, he also supervised the construction of Saint Dunstan's College in Charlottetown in 1848 and its eventual opening on January 15, 1855.

It was built to respond to the needs of Catholic students on the Island, as opposed to Prince of Wales College, which was a majority-Protestant public institution.