Plague, a highly infectious disease caused by Yersinia pestis, has killed millions of people in history and is still active in the natural foci of the world nowadays. Understanding the spatiotemporal patterns of plague outbreaks in history is critically important, as it may help facilitate the prevention and control for potential future outbreaks. This study’s objective was to estimate the effect of the topography, vegetation, climate, and other environmental factors on the Y. pestis ecological niche. A maximum entropy algorithm spatially modelled plague occurrence data from 2004–2018 and the environmental variables to evaluate the contribution of the variables to the distribution of Y. pestis. Our results found that the average minimum temperature in September (–8 °C to +5 °C) and the sheep population density (250 sheep per km²) were influential in characterising the niche. The rim of Qinghai Lake showed more favourable conditions for Y. pestis presence than other areas within the study area. Identifying various factors will assist any future modelling efforts. Our suitability map identifies hotspots and will help public health officials in resource allocation in their quest to abate future plague outbreaks.