A nearby historic site, Carhagouha, marks the spot where an earlier Récollet missionary to Wendake, Father Joseph Le Caron, presided in 1615 over the first Catholic mass conducted in present-day Ontario.

It was at Saint-Louis that Jesuit missionaries Jean de Brébeuf and Gabriel Lalement were captured when the Wendat village was attacked by the Iroquois on March 16, 1649.

Sainte-Marie among the Hurons was established in 1639 by French Jesuits, Fathers Jérôme Lalemant and Jean de Brébeuf in the land of the Wendat.

Arriving in November 1639, the priests erected a makeshift shelter out of "cypress" (probably eastern white cedar) pillars and a birch bark roof, using clay to build the interior walls.

After the arrival of carpenter Charles Boivin, further construction resulted in a chapel, a residence for the Jesuits, a cookhouse, a smithy and other buildings.

A small group of religiously devoted men, also known as donnés (offered, given or gifts), worked at Sainte-Marie among the Hurons, in return for food, clothing, and shelter.

The founding of the mission led to division amongst the Wendat, with conflict between those who converted to Christianity and those who maintained traditional beliefs.

Epidemics of smallpox, which raged from 1634–1640, were brought by the increased number of children emigrating to the colonies with families from cities where the disease was endemic in France, England and the Netherlands.

The weakened Wendat nation was little match for the strengthened Iroquois, who had used their trading alliances with the Dutch to gain firearms.

Owing to the proximity of their deaths to Sainte-Marie, the French recovered the bodies of Brébeuf and Lalemant to be buried at the mission.

On June 16, 1649, the missionaries chose to burn the mission rather than risk it being desecrated or permanently overrun by Iroquois in further attacks.

Father Paul Ragueneau wrote,"We ourselves set fire to it, and beheld burn before our eyes and in less than one hour, our work of nine or ten years.

A severe winter and the constant threat of Iroquois attack eventually forced the French from the area, and they travelled back to New France.