Six Indian Nations have at some time inhabited the Devils Tower region and 22 tribes have been identified as culturally affiliated with the Tower. Some routes are annually closed in order to protect nesting Prairie Falcons. Routes are frequently closed between March and July.

In 2026, while there is no permanent legal ban on climbing Devils Tower, the National Park Service (NPS) implements a voluntary climbing closure during the entire month of June. This period is set aside to show respect for the spiritual and cultural ceremonies of several Plains Tribes, including the Lakota, Cheyenne, and Kiowa, who consider the tower (known as Bear Lodge) to be a sacred site. While the NPS cannot legally prohibit climbing due to the site being on federal land, they strongly encourage climbers to stay off the tower during this month. Approximately 85% of climbers traditionally honor this request. Additionally, temporary mandatory closures can occur at other times of the year, typically from late spring to early summer, to protect nesting prairie falcons. These specific closures are usually restricted to certain "sectors" or faces of the tower where the birds are active, rather than the entire monument, and are strictly enforced to ensure the survival of the fledglings.