Most Native American groups believed in a form of animism in which spirit essence(s) infused forces of nature (e.g., the wind and thunder), many living plants and creatures, and many inanimate objects. This animism created other-than-human persons in which spirits were fused with matter that allowed them to interact with and even influence humans. Art in Western culture tends to denote “imagination”, and many scholars studying Native American art bring a similar perspective to their analyses. However, many Native Americans do not equate art with imagination in the same way, but instead use art to realistically portray these other-than-human persons, even when they are not typically visible in the natural world (e.g., the Southwestern horned-plumed serpent). Here, we apply a cognitive framework to evaluate the interplay of spirits at various levels that were created as Casas Grandes artisans used art as a means of depicting the inherent structure of the Casas Grandes spirit world. In doing so, they created links between ceremonially important objects such as pots and spirits that transformed these objects into newly created animated beings. The art thus simultaneously reflected the structure of the unseen world while also helping to determine the characteristics of these newly created other-than-human persons. One technique commonly used was to decorate objects with literal depictions of spirit beings (e.g., horned-plumed serpents) that would produce a natural affinity among the ceremonial objects and the spirit creatures. This affinity in turn allowed the animated ceremonial objects to mediate the interaction between humans and spirits. This approach transcends a view in which Casas Grandes art is considered symbolically significant and instead emphasizes the art as a component that literally helped create other-than-human collaborators that aided Casas Grandes people as they navigate ontologically significant relationships.