The Patagonian opossum (Lestodelphys halli), the southernmost living marsupial, inhabits dry and open environments, mainly in the Patagonian steppe (between ~32 °S and ~49 °S). Its rich fossil record shows its occurrence further north in Central Argentina during the Quaternary. The paleoenvironmental meaning of the past distribution of L. halli has been mostly addressed in a subjective framework without an explicit connection with the climatic "space" currently occupied by this animal. Here, we assessed the potential distribution of this species and the changes occurred in its geographic range during late Pleistocene-Holocene times and linked the results obtained with conservation issues. To this end, we generated three potential distribution models with fossil records and three with current ones, using MaxEnt software. These models showed a decrease in the suitable habitat conditions for the species, highlighting a range shift from Central-Eastern to South-Western Argentina. Our results support that the presence of L. halli in the Pampean region during the Pleistocene-Holocene can be related to precipitation and temperature variables and that its current presence in Patagonia is more related to temperature and dominant soils. The models obtained suggest that the species has been experiencing a reduction in its geographic range since the middle Holocene, a process that is in accordance with a general increase in moisture and temperature in Central Argentina. Considering the findings of our work and the future scenario of global warming projected for Patagonia, we might expect a harsh impact on the distribution range of this opossum in the near future.