Henry Harmon Spalding was born at Bath, New York, in 1803 and died at Lapwai, Idaho Territory, in 1874. Spalding graduated from the Franklin Academy in Prattsburgh, New York in 1831, and from Western Reserve College in 1833. He attended but did not graduate from Lane Theological Seminary. In 1835 he was ordained by the Presbytery of Bath. Eliza Hart was born in Berlin, Connecticut, in 1807. In 1820 her family moved to Holland Patent, New York. In 1833 she and Spalding were married before he went to Lane Seminary. While there she attended classes in the Hebrew and Greek Bible and theological lectures of Lyman Beecher.

Early in 1836, the Spaldings, under appointment by the American Board of Commissioners for Foreign Missions (ABCFM) to the Osage Indians, met Marcus Whitman who had returned from Oregon to recruit missionaries and settlers. Whitman persuaded the Spaldings to go to the Northwest as Presbyterian missionaries. The Spaldings and Whitman and his bride made a hazardous six months journey, the wives being the first white women to cross the Rocky Mountains. The Spaldings established a mission among the Nez Perces in the Lapwai Valley in present Idaho. They opened a school and set up the first printing press in the Northwest. Spalding also trained the Indians in farming.

After the massacre of the Whitmans in 1847, which the Spaldings escaped, it was twenty-four years before Spalding could return to Idaho as a missionary. The remaining three years of his life were spent in controversy with the Indian agent, but were also fruitful in the work among the Nez Perces and other Indian tribes of the area.