Sinkholes are inherent features of the karst terrain of Greene County, Missouri, that present hazards and engineering challenges to construction/infrastructure development. Analysis of relationships between the spatial distribution of sinkholes and possible influencing factors can help in understanding the controls involved in the formation of sinkholes. The spatial analysis outlined herein can aid in the assessment of potential sinkhole hazards. In this research, Geographic Information System–based ordinary least squares regression (OLS) and geographically weighted regression (GWR) methods were used to determine and evaluate principal factors appearing to influence the formation and distribution of karst sinkholes. From the OLS result, seven out of 12 possible influencing factors were found to exert significant control on sinkhole formation processes in the study area. These factors are overburden thickness, depth to groundwater, slope of the ground surface, distance to the nearest surface drainage line, distance to the nearest geological structure (such as faults or folds), distance to the nearest road, and distance to the nearest spring. These factors were then used as independent variables in the GWR model. The GWR model examined the spatial non-stationarity among the various factors and demonstrated better performance over OLS. GWR model coefficient estimates for each variable were mapped. These maps provide spatial insights into the influence of the variables on sinkhole densities throughout the study area. GWR spatial analysis appears to be an effective approach to understand sinkhole-influencing factors. The results could be useful to provide an objective means of parameter weighting in models of sinkhole susceptibility or hazard mapping.