This article examines a rare sixteenth-century manuscript lectionary (Biblioteca Nazionale Braidense, Manoscritti, AH._X.9) containing Nahuatl translations of Biblical texts, long associated with Bernardino de Sahagún and the Franciscan evangelization project in New Spain. Through interdisciplinary analysis combining ethnohistory, art history, and conservation, the authors illuminate Indigenous roles in colonial knowledge production. The lectionary, in effect, offers a core sample of the intellectual labor of Indigenous peoples involved in its creation: They served as scribes and Biblical translators, as papermakers, and possibly as bookbinders. Unique among the corpus of Nahuatl lectionaries, this manuscript was created from two types of native paper, one for the main text and another for binding reinforcement. Considering the paper as the outcome of pre-Hispanic technologies allows us to expand the field of Indigenous knowledge manifested in the Christian book to include material knowledge, as well as theological and linguistic knowledge. This trinity of knowledge allows us to link the lectionary to Sahagún’s Nahuatl sermonary (Newberry Library Ayer MS 1485) produced at the Colegio de Santa Cruz in Tlatelolco. The lectionary’s preservation of neophytes’ alphabet practice offers singular evidence of the pedagogical practices at the Colegio.