A half-formed purpose to devote themselves to missionary work was rendered stronger by the early deaths of their first three children; and after spending one winter at Lane Theological Seminary, Cincinnati, and being licensed to preach the gospel, Dr. Williamson was appointed by the American Board in the spring of 1834 to visit the Indian tribes west of and near the Mississippi River and north of the State of Missouri. The result was the establishment by the Board of a new mission, of which Dr. Williamson was put in charge. As soon as navigation opened in the spring of 1835, he left Ohio with his family, and until 1846 was stationed at Lac-qui-parle, among the Dakotas, in the western part of what is now the State of Minnesota. In 1846 he removed to Kaposia, five miles below St. Paul, and after the cession of these lands to the government, followed the Dakotas in 1852 to their reservation, and selected as his residence a spot some thirty miles south of Lac-qui-parle. He continued there until the Indian outbreak in 1862, and afterwards made his home at St. Peter, Minn., where he died, June 24, 1879, in his 80th year. His wife died in July, 1872.