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Agassiz’s desert tortoise (Gopherus agassizii) populations are exposed to a variety of anthropogenic threats, which vary in nature, distribution, severity, and frequency. Tortoise management in conservation areas can be compromised when the relative importance of these threats is not well understood. We used HexSim to develop simulation models for desert tortoise populations occupying 2 study areas in the western-central (Superior Cronese in California, USA) and the eastern (Gold Butte-Pakoon in Nevada and Arizona, USA) Mojave Desert, each with a distinct set of site-specific threats. We developed threats models that were parameterized from published information, and conducted independent simulations of threats at varying levels of severity for each study area. Modeled tortoise populations in both study areas were subjected to simulations of threats associated with human presence and subsidized predators. Additional simulated threats in the Superior Cronese model included disease and habitat degradation on land in-holdings, whereas tortoise populations in the Gold Butte-Pakoon model were further exposed to simulations of wildfire, livestock grazing, and feral burros. We used our 2 study area-specific simulation models to rank the threats’ relative importance to desert tortoise population viability. Threats more widely distributed in time and space within the modeled conservation areas significantly limited tortoise population growth more than threats that were patchily distributed or temporally dynamic. Our use of a spatially explicit population model allowed us to evaluate and prioritize the effects of threats over site-specific, dynamic, simulated landscapes, which differed from previous modeling efforts for desert tortoises. Our threat prioritization will inform and improve ongoing management efforts attempting to increase desert tortoise population viability by altering anthropogenic disturbance regimes. (C) 2016 The Wildlife Society.