Congregationalist missionary the Reverend Cushing Eells was born in Massachusetts on February 16, 1810. Eells founded Whitman CollegeExternal in Walla Walla, the oldest educational institution in Washington State, when the Washington Territorial Legislature granted a charter to the Whitman Seminary on December 20,1859. He named the school in honor of fellow missionaries Marcus and Narcissa Whitman, who were killed by Native Americans in 1847. The Whitmans were pioneers who helped open the Oregon Territory to U.S. settlement.

In 1836, the Whitmans founded a mission among the Cayuse Indians at Waiilatpu, seven miles west of present-day Walla Walla. In addition to evangelizing, the missionaries established schools and gristmills and introduced crop irrigation. However, their work advanced slowly, jeopardizing funding. In 1842, in response to a letter ordering the Whitmans to leave Waiilatpu, Marcus Whitman journeyed East and convinced the American Board of Commissioners for Foreign Missions to continue supporting the work of the mission. Returning the following year, he joined the “Great Migration of 1843”—approximately 1,000 settlers traveling to Oregon Territory. Without Whitman’s aid the caravan might not have reached its goal.

With the sudden influx of settlers, tension between Native Americans and the pioneers escalated. Trouble erupted in 1847 when a measles epidemic killed a disproportionate number of Native American children. A practicing physician, Whitman was accused of using magic to eliminate Native Americans in order to make way for new immigrants. Marcus and Narcissa Whitman and twelve other settlers were killed by Cayuse warriors on November 29, 1847. Known as the Whitman Massacre, this event precipitated the Cayuse War—a conflict that lasted until 1850.

Between 1769 and 1823, Spanish Catholics established twenty-one missions among California Indians. Catholic missionaries competed for conversions among the Cayuse in the 1840s.