The Jesuit missionary Claude Dablon inaugurated the original church on Mackinac Island in 1670, and the earliest surviving parish records date back to 1695.

[4] The parish's Jesuit heritage became diluted in the 1740s when a primary focus of the mission outreach, the Odawa (Ottawa) peoples of the Straits of Mackinac, moved in search of fertile farmland from the sandy region around Fort Michilimackinac to new L'Arbre Croche locations southwestward along the Lake Michigan coast.

[4] The Fort Michilimackinac location evolved into service as a parish church for a partly transient population that included many traveling fur traders and voyageurs.

[4] It was during this period of de facto lay leadership, during which time the parish did not have an assigned priest, that the church building was disassembled and moved (under British orders) from Fort Michilimackinac to Mackinac Island, its new permanent home, in 1780–1781.

The general indifference by the new American military authorities to the Catholic faith, led to the temporary disintegration of the church's structure of lay leadership.

[4] After the War of 1812, the parish was saved by a prominent local fur trader, Madeline La Framboise, an Ojibwe who worked with a succession of visiting priests to restore the church's status as a place of worship.