William and Mary (Smith) Williamson, was born at Fair Forest, Union District, South Carolina, on March 8, 1800; in 1805 his father, wishing to set at liberty the enslaved persons which he had inherited, moved to Manchester, Ohio.

He graduated from Jefferson College, Canonsburg, Pennsylvania, in 1820, and soon after began to read medicine with his brother-in-law, Dr. William Wilson, of West Union, Ohio.

On receiving his degree he settled in Ripley, Ohio, where he soon gained a good practice, and was married, April 10, 1827, to Margaret, daughter of Col. James Poage.

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 Native American peoples west of and near the Mississippi River and north of the State of Missouri.

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 Dakota, in the western part of what is now the State of Minnesota.