The present study assessed the co-occurrence of fluoride and arsenic in groundwater of Dharmanagar region (Tripura, India). Co-occurrence of the two toxicants was observed in 59% of the analyzed groundwater samples (n = 71), out of which concentrations of both the toxicants exceeded the World Health Organization drinking water standards in 30% samples. Significant positive correlation (r = 0.6) was observed between groundwater fluoride (<0.005–4.8 mg/l) and arsenic (<0.003–0.044 mg/l) contents. The range of cumulative estimated daily intakes (EDI) in the studied population was: 0.07–0.1 and 0.13–0.18 mg/kg-day for the Central Tendency Exposure (CTE) and the Reasonable Maximum Exposure (RME) scenarios, respectively. The EDI (fluoride) for the children of the study area was already found to reach the ‘Tolerable Upper Intake Level’ (UL) value (0.1 mg/kg-day), and the children are thus at high risk from developing dental fluorosis. Irrespective of the CTE or RME scenario, the hazard index of fluoride (HI_Fluoride = 1.2–3) and that of arsenic (HI_Arsenic = 1.5–5) were always found to be unsafe (HI > 1) in the studied population. The estimated Cumulative Noncancerous Lifetime Hazard Index for simultaneous fluoride and arsenic exposures was calculated to be prominently high (10 and 22 for the CTE and RME scenarios, respectively). The average urinary fluoride and arsenic contents of the studied population was observed to be correlated (r = 0.46 and 0.69) with the groundwater fluoride and arsenic concentrations, respectively. The observed content of urinary fluoride (mean = 3.1 ± 1.2 mg/l) of the studied population was determined to be 65–163% of their total fluoride intakes (1.9–7.2 mg/day). The obtained results are highly alarming and thus for reducing threats to human health, the government should immediately take necessary action for supplying safe drinking water for the residents.