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. The fortified missionary settlement acted as a centre and base of operations for Jesuit missionaries on the outskirts of what is now Midland, Ontario as they worked amongst the Huron. It also provided an example of a functioning European community to the Huron. The mission was built near the Huron settlement of Quieunonascaranas, led by chief Auoindaon.

The mission was initially founded by 18 men. Arriving in November 1639, the priests erected a makeshift shelter out of cypress pillars and a birch bark roof, using clay to build in 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. Sainte-Marie became the Jesuit headquarters in Huronia, from which the Jesuits travelled among the Huron, Petun, Nipissing, Ottawa and Ojibwa peoples.