[2][3] The five-building museum campus was designed by architect Frank Gehry to "dance" with the ancient live oak trees on the 4-acre (1.6-hectare) site.

[4] In August 2005, the museum was damaged during Hurricane Katrina, when a casino barge was washed onto the semi-constructed facility.

Zahner of Kansas City, Missouri, was the subcontractor for the museum's curving structures and metalwork,[5] described as "stainless-steel pods designed to dance among the live oaks" ...[6] On November 8, 2010, three buildings on the east side of the campus opened with outstanding exhibitions, including George Ohr pottery from Gulf Coast collections.

The John S. and James L. Knight Gallery, which will house the George Ohr pottery, is scheduled for completion in 2014.

In July 2011, less than a year after it opened, the Ohr–O'Keefe Museum was facing financial difficulties because revenues were not sufficient to cover operating costs.