The present study aimed to assess chemical risks in the drinking water of inhabitants in the basin of the Tonle Sap Great Lake. Water samples from tube wells (n = 52), dug wells (n = 13), stored rain water (n = 39), ponds/lakes (n = 19), canals/rivers (n = 24), and household pipe water (n = 45) were collected and analyzed for physicochemical properties, as well as microbial and chemical qualities using standard methods. Analytical results revealed that 42.1% of tube wells had As > 10 μg L-1 while 8.3% had Cr > 0.05 mg L-1. Concurrently, 55.2 and 11.8% of tube wells had Cd > 3.00 μg L-1 and Pb > 10 μg L-1, respectively. Moreover, 35.0% of pipe water had Fe > 0.3 mg L-1, whereas 85.7% of tube wells and 69.2% of dug wells had Mn > 0.1 mg L-1. All water sources including pipe water could pose risks of non-carcinogenic effects of chemical mixtures to all exposure groups through their drinking water pathway. Children were at a higher risk of chemical mixtures in their drinking water than adults. This study suggests that advanced treatment technologies should be applied to the current water treatment plants to provide inhabitants with safe drinking water.