This article analyzes Indigenous interpretations and transcultural adaptations of the European Christian Other in Mexico in the first colonial century. In contrast to narratives of a profound spiritual conquest, Indigenous worldviews were largely maintained and Christian practices such as the veneration of saints integrated into this frame. The monasteries and churches built in 16th century Central Mexico by Indigenous artisans under supervision of the mendicant orders are expressions of creative processes combining European with Indigenous art styles. Many decorations and murals show images of flora, fauna, and celestial bodies including the eagle and the sun. This imagery was highly expressive in both European and Indigenous symbolism. I argue that Indigenous artists and practitioners most probably not only associated specific Indigenous religious meanings with this imagery but also interpreted it within the general frame of Indigenous immanent, relational ontology and semiotics.