Large-scale spatial heterogeneity and distribution patterns of limestone soil nutrients in the karst areas of northwestern Guangxi were evaluated in this study, based on regional field survey and laboratory analysis combing with classical statistics and geostatistics. The results showed that pH value of limestone soil had little variation in the karst areas of Northwestern Guangxi, while the variation coefficients of soil nutrients ranged from 30% to 75%, which can be considered as moderate variation. The characteristics of spatial variability differed among soil nutrients. Spherical model, Gaussian model, and linear model were the best-fit model for soil organic matter (SOM), available phosphorus (AP), and available potassium (AK), respectively. However, pH, available nitrogen (AN), total nitrogen (TN), total phosphorus (TP), and total potassium (TK) could be best fitted by exponential model. In addition, SOM, AP, TN, and TP showed moderate spatial autocorrelation, and spatial variability was caused by both random and structural factors. On the other hand, pH, AN, AK, and TK showed weak spatial autocorrelation, and spatial variability was mainly controlled by random factors. The variation range for SOM and TN were large while that for pH, AN, and TK were small. The contents of SOM, TN, TP, and AP exhibited a decreasing trend from west to east but the distribution of pH, AN, AK, and TK did not show any regularity on a regional scale. The correlation analysis demonstrated that, on a large scale, topographic factors (i.e., altitude, slope and rock exposure rate) and vegetation type were important factors affecting the spatial variability of limestone soil nutrients in the karst areas of northwestern Guangxi.