A major public health concern in Mexico is the natural contamination of groundwater with fluoride and arsenic. Therefore, this work aimed to evaluate the magnitude of human health risk after determining fluoride and arsenic concentrations in groundwater samples (n = 50) from the Metropolitan area of the city of San Luis Potosi, Mexico. Fluoride levels in water were determined via a potentiometric method using an ion-selective electrode. Arsenic concentrations in water samples were determined with an Atomic Absorption technique. Subsequently, a probabilistic health risk assessment was developed (Monte Carlo Analysis). Fluoride levels in water ranged from 0.20 to 3.50 mg/L. For arsenic, the mean level found in the assessed water samples was 15.5 ± 5.50 μg/L (range: 2.50–30.0 μg/L). In addition, when the probabilistic health risk assessment was completed, a mean HI (cumulative hazardous index) of higher than 1 was detected, indicating a high NCR (non-carcinogenic risk) for children and adults. According to the results found in this study, exposure protection campaigns are imperative in the Metropolitan area of the city of San Luis Potosí, Mexico, to successfully diminish exposure to arsenic and fluoride and, as a consequence, decrease the NCR in the population living in that region of Mexico.