The museum's permanent collection is comprised of over 8,000 objects with a strong focus on American art of the 19th and 20th centuries. European art ranging from the 15th century to the present includes French works from the 19th and 20th centuries and European modernists and Surrealists. Also included are contemporary works, photography, and special collections of Asian works. The museum hosts an average of 16 exhibitions a year.
Located in the Centennial Complex on the University of Wyoming campus, the building's design is an abstract representation of Western history and culture. The five-story copper cone, which houses the American Heritage Center, is reminiscent of a mountain peak, while the brick extension that houses the Art Museum galleries represent the rendezvous sites of the pre-settled West. The rotunda, a circular room reminiscent of an ancient Native American kiva, serves as a transition between the cone and the rectangular galleries.