The Palouse (Palus) lived in three main regional bands, composed of several village-based groups: The ancestral people were nomadic, following food sources through the seasons.

In the latter half of the nineteenth century, the United States Army captured and slaughtered hundreds of tribal horses to cripple the tribe during the Indian Wars.

Lewis and Clark presented one of the expedition's silver peace medals to paramount Chief Kepowhan.

After Kepowhan, during the decades 1830', 1840', 1850, Wattaiwattaihowlis (Kepowhan's son and probably principal chief), Kahlotus (known also as Quelaptip and Talatuche, chief of the Upper Palouse), Soei (chief of the Middle Palouse), Nehtalekin (called also Hahtalekin the Elder), Tilcoax (chief of the Lower Palouse), Hinmahtutekekaikt alias "James" (one among the first to be Christianized, friend to Henry H. Spalding and Marcus Whitman, often associated to the Nimiipu band of Hollolsotetote), were the leaders until the Isaac I. Stevens Treaty in 1855, when the Palouse refused to take part but sent, as observers, Kahlotus (already a good friend to Marcus Whitman), Tilcoax (a war chief) and Slyotze; "Old" Hathalekin and Tilcoax led the Palouse warriors against the U.S. troops during the Cayuse's uprising in 1847–1848, defeating col. Cornelius Gilliam and his "Oregon Volunteers" on the Tucannon Creek (March 14–15, 1848).

Husishusis Kute, chief of the Wawawai Palouse, and "Young" Hathalekin (also known as Taktsoukt Jlppilp), war-chief, led a small Palouse band as allies of the last free Nimiipu of Heinmot Tooyalaket alias "Chief Joseph"; "Young" Hathalekin died fighting on August 9, 1877, at Big Hole; Husishusis Kute surrendered with Heinmot Tooyalaket on October 5, 1877.