The Whitman massacre (also known as the Walla Walla massacre and the Whitman Incident) was the murder of Washington missionaries Marcus Whitman and his wife Narcissa, along with eleven others, on November 29, 1847. They were killed by members of the Cayuse tribe who accused Whitman of having poisoned 200 Cayuse in his medical care. The incident began the Cayuse War. It took place in southeastern Washington state near the town of Walla Walla, Washington and was one of the most notorious episodes in the U.S. settlement of the Pacific Northwest. Whitman had helped lead the first wagon train to cross Oregon's Blue Mountains and reach the Columbia River via the Oregon Trail, and this incident was the climax of several years of complex interaction between him and the local Native Americans. The story of the massacre shocked the United States Congress into action concerning the future territorial status of the Oregon Country. The Oregon Territory was established on August 14, 1848.

The killings are usually ascribed in part to a clash of cultures and in part to the inability of Whitman, a physician, to halt the spread of measles among the Natives. The Cayuse held Whitman responsible for subsequent deaths. The incident remains controversial to this day; the Whitmans are regarded by some as pioneer heroes, while others see them as settlers who had attempted to impose their religion on the Natives and otherwise intrude, even allegedly poisoning them.In 2021, Blaine Harden publishsed "Murder at the Mission" to explore how the Whitman massacre myth was created by an erratic, self-promoting Presbyterian missionary named Henry Harmon Spalding. Although Spalding had " periodic bouts of irrationality" and "fellow missionaries wrote countless letters about his erratic, spiteful, and annoying behavior," his ability to persuade the US Senate to print an official pamphlet about Whitman created both a myth and additional reasons to remove Native people from their tribal lands.