Arsenic (As) contamination in groundwater represents a major global health threat, potentially impacting billions of individuals. Elevated As concentrations are found in river floodplains across south and southeast Asia, as well as in the inland basins of China, despite varying sedimentological and hydrogeochemical conditions. The specific mechanisms responsible for these high As levels remain poorly understood, complicating efforts to predict and manage the contamination. Applying hydro-chemical, geological, and soil parameters as explanatory variables, this study employs multiple linear regression (MLIR) and random forest regression (RFR) models to estimate groundwater As concentrations in these regions. Additionally, random forest classification (RFC) and multivariate logistic regression (MLOR) models are applied to predict the probability of As levels exceeding 10 μg/L in the Hetao Basin (China) and Bangladesh. Model validation reveals that RFR explains 80% and 70% of spatial variability of As concentration in the Hetao Basin and Bangladesh, respectively, outperforming MLIR, which accounts for only 35% and 32%. Similarly, RFC outperforms MLOR in predicting high As probability, achieving correct classification rates of 98.70% (Hetao Basin) and 98.25% (Bangladesh) on training datasets, and 82.76% (Hetao Basin) and 91.20% (Bangladesh) on validation datasets. The performance of the MLOR model on the validation set yields accuracy rates of 81.60% and 72.18%, respectively. In the Hetao Basin, Ca2+, redox potential (Eh), Fe, pH, SO42−, and Cl− are key predictors of As contamination, while in Bangladesh, soil organic carbon (SOC), pH, and SO42− are significant predictors. This study underscores the potential of random forest (RF) models as robust tools for predicting groundwater As contamination.