The onset of Spanish imperial rule in Mexico in 1521 had profound consequences well beyond the political and cultural spheres. It also altered Mexico’s environment, reconstituting the region’s ecology as new fauna, flora, and microorganisms were added and as the population dynamics of native Mexican biota fluctuated in response to Old World arrivals. While the consequences of myriad interactions between native and non-native species were vast and complex, it was the decimation of indigenous persons by pathogens that was one of the first biological consequences of colonization (in fact, occurring first in 1520, one year before the fall of the Aztec state) and one of the most important. Mexican human populations were reduced by 80 to 90 percent, effecting cascading ecological consequences across the physical and biological geography of Mexico. Forests regenerated, terraced slopes degraded, and much of the Mexican landscape lost its anthropogenic aspect. Simultaneously, ungulate introductions transformed Mexican flora and likely initiated soil erosion in some regions that, when transported to fluvial environments, disrupted the flow of rivers. On the other hand, pigs, sheep, goats, horses, and other ungulates altered plant communities through selective seed dispersion. New economic pursuits such as brick making and silver mining increased demand for heat energy that, in an unprecedented manner, encouraged intensive forest usage and, probably, regional deforestation, although empirical data on historical forest cover are still lacking. Severe climate variability, of a scale not experienced for at least five hundred years and perhaps many millennia, occurred simultaneously with colonial-induced ecological change. A significant conquest-era drought was followed by one of the coolest and wettest periods of the Holocene; a strong pluvial in the Mexican context lasted from 1540 to around 1620. Subsequent anomalies of both temperature (cold) and precipitation (either wet or dry) occurred in the 1640s and 1650s, and from the 1690s until about 1705. Together, these climate anomalies are known as the core Little Ice Age, and initiated agrarian transitions, hazardous flooding, prolonged droughts, epidemics, epizootics, and recurring agrarian crises that destabilized human health and spurred high rates of mortality. Soil degradation and suppressed forest cover are also likely outcomes of this process. Although debate abounds regarding the timing, extent, and causes of soil and water degradation, there is little doubt that extensive degradation occurred and destabilized late-colonial and early-Republic societies.