Founded in 1841 and designed as an ongoing village for Catholic Salish Indians, St. Mary's was the first permanent settlement made by non-indigenous peoples in what became the state of Montana.

Lakotas near Ash Hollow (Nebraska) killed a third group sent to make the same request in 1837, including Ignace.

[4]: 213  In 1839, two Iroquois Indians met Father De Smet at Council Bluff, by chance, and they relayed the request again.

In July 1840, Father De Smet was greeted by more than 1,000 Salish and Pend d'Oreille Indians in Pierre's Hole.

[5]: 21  Accompanying him to the Bitterroot Valley were Fathers Gregory Mengarini and Nicholas Point, as well as Brothers Joseph Specht, William Claessens, and Charles Huett.

[5]: 30  As construction began under the supervision of Pierre-Jean De Smet, he described St. Mary's and the Salish workforce as follows: The women hewed down the timber, assisted by their husbands, with the greatest alacrity and expedition, and in a few weeks we had constructed a log church, capable of holding 900 persons.

To ornament the interior, the women placed mats of a species long grass, which were hung on the roof and sides of the church, and spread over the floor,-- it was then adorned with festoons formed of branches of cedar and pine.

The buildings include the chapel with an attached residence, the infirmary, a dovecote, a cabin with Salish artifacts, and a visitor's center that contains a museum, a research library, an art gallery, and a gift shop.