The Flathead were the easternmost of the Plateau Indians. Like other tribes that regularly traversed the Rocky Mountains, they shared many traits with nomadic Plains Indians. The Flathead acquired horses in great numbers and mounted annual fall expeditions to hunt bison on the Plains, often warring with tribes that were permanent residents of the area. Traditional Flathead culture also emphasized Plains-type warfare and its honors, including staging war dances, killing enemies, counting coups (touching enemies to shame or insult them), kidnapping women and children, and stealing horses.

Before colonization, the Flathead usually lived in tepees; the A-framed mat-covered lodge, a typical Plateau structure, was also used. Western Flathead groups used bark canoes, while eastern groups preferred the round bison-skin vessels known as bullboats that were typical of the Plains. Fishing was important among the Flathead, as it was among other Plateau tribes.

Traditional Flathead religion centred on guardian spirits, with whom individuals communicated in visions; a spirit could bring good fortune and health to the person it guarded or disease and misfortune to others. Shamanism was also important to traditional religious and healing practices.

Early 21st-century population estimates indicated more than 4,000 Flathead descendants. Most lived on the Flathead Reservation (formally the Confederated Salish and Kootenai Tribes of the Flathead Reservation) in western Montana, the fourth largest reservation within the United States.