The museum headquarters and public spaces are located at 1680 East 15th Avenue in a building inspired by the design of Pacific Northwest Native longhouses.

The museum traces its origins to the creation of the University of Oregon in 1876, when state geologist Thomas Condon was hired as one of the first three UO professors, bringing his extensive fossil collection with him.

[2] Since Cressman retired in the 1960s, the museum has had a series of distinguished directors, including J. Arnold Shotwell, Alice Parman, Don Dumond, C. Melvin Aikens, Jon Erlandson, and currently Todd J. Braje.

[7] that are among the oldest shoes in the world (~10,000 years old); extensive ethnographic collections from cultures worldwide, including over 1500 Native American baskets; and thousands of comparative specimens from modern or historical birds (and their eggs and nests), mammals, reptiles, marine and freshwater shells, and other organisms.

Tribal members worked closely with museum staff in designing exhibits and creating replicas for displays that highlight the deep history of Native American tribes in four geographic regions of Oregon: the Northwest Coast, Columbia Plateau, Great Basin, and Willamette Valley.