This article presents and analyzes the Indian-Christian murals of Santa María Xoxoteco, a small 16th Century Augustinian chapel in Central Mexico. The murals were part of an extensive production of Christian art by native artists, which flourished in the 16th Century in the wake of the missionaries’ efforts to convert the newly conquered native people to Catholicism. In this article, I follow recent scholars’ attempts to move beyond the earlier dualist focus on either a native or a Christian origin for this genre of art, and instead view the murals as independent expressions of Colonial religion by emphasizing the interaction of the murals with other motifs in colonial art and texts. I begin with a historical remark on the mission methods brought to the New World by the Mendicant orders. Next, I present the murals and discuss the Christian, native and colonial contents of the motifs, as well as the ways the native population may have perceived these motifs. Finally, I offer a brief theoretical reflection on the study of Colonial art.