The purpose of this study was to determine the fluoride concentrations in drinking water of the Khaf County in Eastern Iran. Moreover, health risk assessment of three age groups (children, teens and adults), sensitivity analysis and uncertainties in the risk estimates were carried out using Monte Carlo simulation. For this reason, drinking water in 33 villages and 5 cities of the Khaf County were collected during March to September 2018. Fluoride contents in drinking water samples were assayed by using a HACH-DR6000 spectrophotometer. Fluoride content in drinking water from urban area and rural area ranged from 0.50 to 0.91 mg L−1 and 0.24 to 2.31 mg L−1. Among the population of the 33 villages, about 17 villages, corresponding to 51%, receive ﬂuoride concentrations less than 0.5 mg L−1 (minimum allowable concentration recommended by WHO), while the population of 4 villages, corresponding to 12%, receive ﬂuoride concentrations higher than 1.5 mg L−1 (the maximum allowable concentration of fluoride in drinking water recommended by the WHO). Moreover, our findings showed that the drinking water ingestion rate, ﬂuoride concentration in water, and the fraction of skin in contact with water were the most important variable in calculating the Hazard quotient (HQ).