[2] The museum's galleries are in Dyche Hall on the university's main campus in Lawrence, Kansas.

Among its more than 350 separate exhibits, the museum is famous for its Panorama of North American Wildlife, part of which represented Kansas in the 1893 World's Colombian Exposition in Chicago, and was the impetus for the funding and construction of Dyche Hall and its Natural History Museum between 1901 and 1903.

Modeled after a church in France, Dyche Hall was designed to house the Panorama in the "apse" of the entrance gallery.

The museum is also renowned for Comanche, the only survivor on the U.S. Cavalry side of the Battle of the Little Bighorn; for its extensive exhibits of plesiosaurs, mosasaurs, pterosaurs, and other fossils from the Kansas Chalk; and most recently for its newest displays of mammalian skulls, the parasites of sharks and rays, and the pre-Columbian archaeology of Costa Rica.

The Institute's collections, faculty-curators, staff and students are housed in six buildings across the KU campus, with the most recent expansion occurring in 2006–2007, when the Division of Entomology, along with parts of the ornithological and mammal collection, were moved to a new facility on the university's West Campus.