This dissertation examines how Nahuas used their Franciscan monastery—its spaces, imagery, and institutional structure—to challenge Spanish hegemony in the Atlixco Valley, the bread-basket of sixteenth century New Spain. It concentrates on the artistic and sociopolitical interventions of Indigenous Nahuas within the public and private spaces of the monastery of San Martín de Tours, Huaquechula, Mexico to upend a frequent assumption that Indigenous people engaged with Christianity on a superficial level and predominately through outdoor, public rituals. Analysis of the Huaquechula monastery’s multiple topographies repositions Nahuas as insiders, physically and socio-politically situated within the monastery to negotiate power asymmetries and advance Nahua interests and futures. My chapters follow Nahuas from the most public to the most private sacred spaces within the Huaquechula monastery to trace two distinct but overlapping issues: the development of a sixteenth century Nahua mural painting tradition, and Christian art and architecture as an expression of Indigenous political and territorial self-determination. In so doing, my dissertation demonstrates that Nahuas were not passive recipients of the large-scale changes to their built and sociopolitical environments in the wake of the Spanish conquest. Instead, Nahuas deployed the monastery’s art and architecture to negotiate a future for their altepetl, one that made Nahuas indispensable to the spiritual and administrative operations of the monastery of San Martín de Tours. The Huaquechula monastery raises a fundamental question for the study of the colonial Americas: how does Indigenous Christian art and architecture evince artistic and political agency? Traditionally, this question has been answered by centering specific objects and texts that have discernible marks of Indigeneity. The case of the Huaquechula monastery is instructive in this instance because the standard sources for investigating Indigenous agency are extremely limited. As a result, the Huaquechula monastery seems to be an unlikely place to unearth Indigenous agency. I overcome this impasse by shifting the analytical lens from form to context. This dissertation investigates the Huaquechula monastery within a fifty-year interval between 1535-1585 through a comparative analysis of four spaces: the monastery patio (chapter 1), the lower cloister (chapter 2), the church interior (chapter 3), and the upper cloister (chapter 4). Considered together, the Huaquechula monastery illuminates how Nahuas used Christian art and architecture to address the ever-changing configurations of Spanish colonial power. An art historical investigation of the Huaquechula monastery is thus an opportunity to critically engage with the assumptions implicit in current models of Indigenous art history in the Americas, and broaden the analytical toolkit to encompass approaches grounded in Indigenous worldviews.