The current study explored the epidemiological associations between the 2016/18 highly pathogenic avian influenza (HPAI) epidemics and spatial factors, including the distance from a poultry farm to the closest groundwater source, migratory bird habitat, eco-natural area, and poultry farm altitude. We included 14 spatial factors as independent variables. The variables were used in the original continuous measurement format. In total, 288 poultry farms (144 HPAI-confirmed and 144 non-confirmed) were used as the dependent variable. In addition, the variables’ continuous measurement was converted to a categorical measurement format by using a general additive model. For risk factor analysis based on the continuous measurements of spatial factors, the non-graded eco-natural area distance (odds ratio [OR]: 1.00) and the grade one eco-natural area distance (OR: 0.99) were statistically significant independent variables. However, in the risk factor analysis based on the categorical measurement format of the spatial factors, the non-graded eco-natural area distance (OR: 0.08) and poultry farm altitude (OR: 0.44) were statistically significant independent variables in both a univariate and multiple logistic regression model. In other words, when a poultry farm was located far from the non-graded eco-natural area or in a highland area, the likelihood of an HPAI epidemic would decrease. From an HPAI control perspective, it is recommended that the government apply increased levels of biosecurity measures, such as bird-nets, fences, intensive disinfection of equipment, and regular bird health monitoring, for poultry farms located near non-graded eco-natural areas or in a lowland area.