In the early 19th century, the Coeur d'Alene Indians had heard of these powerful "medicine men" in black robes with a book and wanted some of these men for their own tribe. They sent men east to St. Louis, and in 1842 Father Pierre-Jean De Smet responded to the request and came to the area. Fr. Nicholas Point and Br. Charles Duet came and helped to pick a mission location. The first was along the St. Joe River, but was subject to flooding. In 1846, they moved it to the current location.

In 1850, the church was taken over by Antonio Ravalli, who began designing the new mission building. He made sure that the building was constructed by the Indians themselves, so that they could feel part of the church. It was built using the wattle and daub method, and was finished some three years later, without using a single nail.

In time, the mission became an important stop for traders, settlers, and miners taking on the role as a hospitality and supply station. It was also a working port for boats heading up the Coeur d'Alene River.