The Flatheads were the easternmost of the Plateau Indians (Plateau Indian); like other tribes that regularly traversed the Rocky Mountains, they shared many traits with nomadic Plains Indians (Plains Indian). The Flatheads 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 honours, 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 had bark canoes, while eastern groups used the bison-skin tubs 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 (guardian spirit), 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.