The widespread presence of arsenic (As) and fluoride (F−) in groundwater poses substantial risks to human health on a global scale. These elements have been identified as the most prevalent geogenic contaminants in groundwater in northern Mexico. Consequently, this study aimed to evaluate the human health and ecological risks associated with the content of As and F− in the Meoqui-Delicias aquifer, which is in one of Mexico's most emblematic irrigation districts. Concentrations of As and F− were measured in 38 groundwater samples using ICP-MS and ion chromatography, respectively. Overall, these elements showed a similar trend across the aquifer, revealing a positive correlation between them and pH. The concentration of As and F− in the groundwater ranged from 5.3 μg/L to 303 μg/L and from 0.5 mg/L to 8.8 mg/L, respectively. Additionally, the levels of As and F− surpassed the established national standards for safe drinking water in 92% and 97% of samples, respectively. Given that groundwater is used for both agricultural purposes and human activities, this study also assessed the associated human health and ecological risks posed by these elements using Monte Carlo simulation and Species Sensitivity Distribution. The findings disclosed a significant noncarcinogenic health risk associated with exposure to As and F−, as well as an unacceptable carcinogenic health risk to As through water consumption for both adults and children. Furthermore, a high ecological risk to aquatic species was identified for F− and high to medium risks for As in the sampling sites. Therefore, the findings in this study provide valuable information for Mexican authorities and international organizations (e.g., WHO) about the adverse effects that any exposure without treatment to groundwater from this region represents for human health.