Following the Lewis and Clark expedition and contact with other European explorers and traders, the Nez Perce sent representatives to St. Louis to learn more about the religion of these newcomers. News of their visit to General William Clark was widely reported by the Methodist press in New England and seen by the church as a "Macedonian Cry" for missionaries in the far West.
In 1833, the Revered Jason Lee was ordained as "Missionary to the Flathead Indians" and charged with setting up a mission in the Oregon Country. Accompanied by four men (Lee's nephew Rev. Daniel Lee, teacher Cyrus Shepard and laymen Courtney Walker and Philip Edwards), the men traveled overland with trader Nathaniel Wyeth, several naturalists and fur trappers. They arrived at Fort Vancouver on September 15, 1834 and were soon convinced by Dr. John McLoughlin to settle in the Willamette Valley.
Their original mission station, which came to be known as “Mission Bottom,” was located about 13 miles north of Salem at what is now Willamette Mission State Park .
The original party of men soon realized that they could not tend to their missionary work and support themselves and the students they took care of at the mission without help. They soon sent for reinforcements, especially asking for women and skilled laymen to help in the mission field. Three separate reinforcements of missionaries arrived, bringing doctors, farmers, blacksmiths and carpenters as well as single women intended to be the brides of the single missionaries.
Just as the missionary population grew, so did the mission field. During their ten years of operation the Oregon Mission added five independent mission stations, including those at The Dalles, Clatsop Plains, Oregon City, Chemeketa (Salem), Nisqually (near Tacoma). A sixth station was planned for southern Oregon, but was never established.