Abstract Background Malaria remains an important public health concern in China and is particularly serious in Yunnan, a China’s provincial region of high malaria burden with an incidence of 1.79/10 5 in 2012. This study aims to examine the epidemiologic profile and spatiotemporal aspects of epidemics of malaria, and to examine risk factors which may influence malaria epidemics in Yunnan Province. Methods The data of malaria cases in 2012 in 125 counties of Yunnan Province was used in this research. The epidemical characteristics of cases were revealed, and time and space clusters of malaria were detected by applying scan statistics method. In addition, we applied the geographically weighted regression (GWR) model in identifying underlying risk factors. Results There was a total of 821 cases of malaria, and male patients accounted for 83.9% (689) of the total cases. The incidence in the group aged 20–30 years was the highest, at 3.00/10 5 . The majority (84.1%) of malaria cases occurred in farmers and migrant workers, according to occupation statistics. On a space-time basis, epidemics of malaria of varying severity occurred in the summer and autumn months, and the high risk regions were mainly distributed in the southwest counties. Annual average temperature, annual cumulative rainfall, rice yield per square kilometer and proportion of rural employees mainly showed a positive association with the malaria incidence rate, according to the GWR model. Conclusions Malaria continues to be one of serious public health issues in Yunnan Province, especially in border counties in southwestern Yunnan. Temperature, precipitation, rice cultivation and proportion of rural employees were positively associated with malaria incidence. Individuals, and disease prevention and control departments, should implement more stringent preventative strategies in locations with hot and humid environmental conditions to control malaria.