Scholars attribute the growth and decline of Classic period (AD 200–900) settlements in the semi-arid northern frontier zone of Mesoamerica to rainfall cycles that controlled the extent of arable land. However, there is little empirical evidence to support this claim. We present phytolith, organic carbon, and magnetic susceptibility analyses of a 4000-yr alluvial record of climate and human land use from the Malpaso Valley, the site of one such Classic frontier community. The earliest farming occupation is detected around 500 BC and appears related to a slight increase of aridity, similar to the level of the modern day valley. By AD 500, the valley's Classic period Mesoamerican settlements were founded under these same dry conditions, which continued into the Postclassic period. This indicates that the La Quemada occupation did not develop during a period of increased rainfall, but rather an arid phase. The most dramatic changes detected in the valley resulted from the erosion associated with Spanish Colonial grazing and deforestation that began in the 16th century. The landscape of the modern Malpaso Valley is thus primarily the product of a series of intense and rapid transformations that were concentrated within the last 400 yr.