Missionaries Dr. Marcus Whitman, his wife Narcissa, and 15 others are killed by Cayuse and Umatilla Indians, causing the Cayuse War.

Marcus Whitman was an American physician and missionary. He is most well known for leading American settlers across the Oregon Trail, unsuccessfully attempting to Christianize the Cayuse Indians, and was subsequently killed by the Cayuse Indians in an event known as the 1847 Whitman massacre, over a misunderstanding, resulting in the beginning of the Cayuse war (1847–1855).

The Whitman massacre was the killing of American missionaries Marcus and Narcissa Whitman, along with eleven others, on November 29, 1847. They were killed by a small group of Cayuse men who suspected that Whitman had poisoned the 200 Cayuse in his medical care during an outbreak of measles that included the Whitman household. The killings occurred at the Whitman Mission at the junction of the Walla Walla River and Mill Creek in what is now southeastern Washington near Walla Walla. The massacre became a decisive episode in the U.S. settlement of the Pacific Northwest, causing the United States Congress to take action declaring the territorial status of the Oregon Country. The Oregon Territory was established on August 14, 1848, to protect the White settlers.

The Cayuse War (1847–1855) was an armed conflict between the Cayuse people of the Northwestern United States and settlers, backed by the U.S. government. The conflict was triggered by the Whitman massacre of 1847, where the Cayuse attacked a missionary outpost in response to a deadly measles epidemic that they believed was caused by Marcus Whitman. Over the next few years, the Provisional Government of Oregon and later the United States Army battled the Native Americans east of the Cascades. This was the first of several wars between the Native Americans and American settlers in that region that would lead to the negotiations between the United States and Native Americans of the Columbia Plateau, creating several Indian reservations.