The Potawatomi were semisedentary, living in agricultural villages in summer and separating into smaller family groups in autumn as they moved to their winter hunting grounds. Men hunted and fished; women planted and harvested crops and collected wild plant foods. Village dwellings were large bark-covered houses or dome-shaped wickiups (wickiup) or wigwams; these were also used at winter sites. The Potawatomi were divided into several politically independent territorial bands that were linked by kinship and language. Clans whose members traced their descent from a common ancestor through the male line were distributed among the various bands, and clan intermarriage served to unify each band.

Crowded by settlers, the Potawatomi ceded their lands and moved west of the Mississippi River at the beginning of the 19th century. Many tribal members who resided in Indiana refused to leave until they were driven out by the U.S. military, and some of them escaped into Canada. In 1846 most Potawatomi were again displaced, this time to a Kansas reservation where they became known as the Prairie band. Over the course of their westerly movements, the tribe borrowed cultural features from the Plains Indians (Plains Indian), notably communal bison hunts. In the late 1860s many of the Kansas band moved to Indian Territory (now Oklahoma), where they were known as the Citizen Potawatomi.

Early 21st-century population estimates indicated approximately 26,000 individuals of Potawatomi descent.