ABSTRACT Art history’s center-periphery paradigm holds metropolitan centers as the originators of artistic models that the periphery copies. Accordingly, European artworks were the primary models for colonial Latin America’s artists who dutifully copied them. Scholarship that accounts for complex artistic negotiations characteristic of colonial societies complicates the long-held view of colonial Latin America as a replicative artistic periphery to Europe. It recognizes mutually constitutive relationships between different groups and artistic practices in the Spanish imperial order. This article highlights select examples of cross-cultural artistic interactions in colonial Mexico and argues that they often operated outside the European/Renaissance preoccupation with artistic originality/innovation as it is characterized in the artist biography genre of early modern Europe. Significantly, Christian global designs were the justification for Spanish power in the Americas, and colonial religious art has often been used to measure the success of that order. Accounting for the strategic copresence of European and Indigenous cosmologies and aesthetics in colonial visual culture is crucial to developing a more rounded and critical understanding of the Christian colonial order in Latin America. It also offers one alternative to the binary and largely unidirectional center-periphery model by highlighting the multidirectional flow of ideas, beliefs, and forms.