The tribes that lived near the Columbia River were enthusiastic about the "blackrobes" and their teachings. So much so that Father DeSmet, a Jesuit priest from Belgium, wrote his superiors in 1840 that he needed more priests to minister to the local Indian tribes. The Jesuits were known as blackrobes because of the black robes they wore. Father DeSmet made the long journey back to Europe to find the Jesuit priests he needed, and returned five years later with two men: Father Anthony Ravalli and Father Hoecken.
In 1845 the newly arrived Father Rivalli, with the help of local Indians, built a small mission from “rough logs and brush.” In these early years St. Paul's was a seasonal church. Father Ravalli would make the two-day journey from the St. Ignatius Mission in Cusick to St. Paul's during the fishing season to minister to the large gatherings of tribes.
In 1847 a permanent church was built near the temporary building. It featured glass windows and walls covered with white mud, not unlike the nearby Fort Colville. The building served as both a place of worship and living quarters. With two wood-burning stoves, it became possible for a priest to live comfortably at St. Paul's year-round. During his tenure, which lasted until 1851, Father DeVos baptized 491 people, held 123 marriage masses, and shepherded 99 souls to the hereafter.
The 1860s were a time of growth and change in and around St. Paul's. The mission had new stained glass windows installed and the new priest, Father Joset, saw an increase in the population of Catholic settlers. Within the decade two new churches had been built closer to the center of the growing community. In the 1870s the opening of an Indian boarding school in Kettle Falls and the closing of the trading post further reduced the need for St. Paul's. The night of August 14, 1875, the lamps were put out for the last time.
The mission sat forgotten until the 20th century. By 1938 the mission's walls could no longer stand on their own and the roof and floor were gone. Restoration efforts began that year under the leadership of Father George. Working with the local Knights of Columbus, he set out to restore the mission to its former glory. The organization used historic tools and techniques to make the new building match the original as much as possible: They hand-sawed logs and even used reproduction nails and hardware. The Mission today stands on its original quartzite foundation.
In 1951 St. Paul's was gifted to the state of Washington, which transferred ownership to the National Parks Service in 1974. In that same year St. Paul's was placed on the National Register of Historic Places.