Spatiotemporal variations of fluoride (F) from 2003 to 2010 in groundwater of Larestan and Gerash region in Iran were monitored employing Mann-Kendall trend test and a geospatial information system (GIS). The annual precipitation had a negative but not significant relation with the mean concentrations of F in the wells of eight cities (Pearson's r = -0.512, p = 0.195) and thirty-one villages (r = -0.545, p = 0.259) for the eight-year period. Results of Mann-Kendall trend test revealed that there is a trend in the series of one city and eleven village's individual-wells for the eight-year period (significant level alpha = 0.05). Moreover, spatiotemporal variations of fluoride were relatively constant over the years. Besides, in 2003 to 2010, 62.8, 63.2, 63.4, 62.8, 62.4, 62.7, 58.9, and 59.5 percent of the Larestan and Gerash region areas had fluoride concentrations beyond the maximum permissible standard F level of 1.4 mg/l. Accordingly, effective protective measures, cost-effective interventions, and compliance monitoring—monthly monitoring—should be considered, especially in unsafe contaminated areas up to achieve a standard level.