White-nose syndrome, a novel fungal pathogen spreading quickly through cave-hibernating bat species in east and central North America, is responsible for killing millions of bats. We developed a stochastic, stage-based population model to forecast the population dynamics of the endangered Indiana bat (Myotis sodalis) subject to white-nose syndrome. Our population model explicitly incorporated environmentally imposed annual variability in survival and reproductive rates and demographic stochasticity in predictions of extinction. With observed rates of disease spread, >90% of wintering populations were predicted to experience white-nose syndrome within 20 years, causing the proportion of populations at the quasi-extinction threshold of less than 250 females to increase by 33.9% over 50 years. At the species’ lowest median population level, ca. year 2022, we predicted 13.7% of the initial population to remain, totaling 28,958 females (95% CI = 13,330; 92,335). By 2022, only 12 of the initial 52 wintering populations were expected to possess wintering populations of >250 females. If the species can acquire immunity to the disease, we predict 3.7% of wintering populations to be above 250 females after 50 years (year 2057) after a 69% decline in abundance (from 210,741 to 64,768 [95% CI = 49,386; 85,360] females). At the nadir of projections, we predicted regional quasi-extirpation of wintering populations in 2 of 4 Recovery Units while in a third region, where the species is currently most abundant, >95% of the wintering populations were predicted to be below 250 females. Our modeling suggests white-nose syndrome is capable of bringing about severe numerical reduction in population size and local and regional extirpation of the Indiana bat.