After being forced to sign a treaty of land cessions, Kamiakin organized alliances with 14 other tribes and leaders, and led the Yakima War of 1855–1858.

He threatened leaders of several tribes to remove the Natives by force from the area east of the Cascades and bordering the Columbia River if they did not sell their lands.

The leaders agreed on wanting to resist encroachment by American settlers and government officials in the Washington Territory.

In 1855 Kamiakin convened a council in Eastern Oregon, with representatives from all of the tribes in the Grande Ronde Valley, in order to discuss how best to deal with the invaders and keep their lands.

The other chiefs eventually pressured Kamiakin into signing the treaty "as an act of peace;" it established the Yakama reservation.

Ranchers led by William Henderson repeatedly tried to drive Kamiakin from his ancestral lands, but Robert Milroy, superintendent of Indian Affairs, intervened.

"[5] On the year anniversary of his death, according to his people's customs, his son (Tesh Palouse Ka-mi-akin) opened his father's grave and wrapped his remains in a new blanket.

Several years later, when Kamiakin's body was exhumed in order to be reburied elsewhere, it was discovered that "the head and shoulders had been cut off and removed",[6] probably for "public exhibition" as a curiosity.