Classical scrapie is a transmissible spongiform encephalopathy that attacks the central nervous system of sheep and goats. Since its discovery in the 18th century, the disease has caused enormous economic losses and public health impacts in continental Europe. In the late 20th century, classical scrapie began to spread to places, such as Asia and the Americas, becoming a disease of global concern. In this study, based on prion occurrence records and high-resolution environmental layers, a risk assessment of classical scrapie in China was performed using a maximum entropy model. The model achieved an area under the curve value of 0.906 (95% confidence interval, 0.0883–0.0929). Sheep distribution density, road density, goat distribution density, minimum temperature of the coldest month, port density, and precipitation of the driest quarter were identified as important factors affecting the occurrence of classical scrapie. The risk map showed that potential high-risk areas in China were mainly located in Northeast China, North China, and Northwest China. This study can provide a valuable reference for the prevention of classical scrapie in China. According to the environmental variables and risk areas of classical scrapie, implementing monitoring and early warning measures in these areas is recommended to reduce the possibility of classical scrapie occurrence and transmission.