Water and sediment samples affected by mining activities were collected from three lakes in Bolivia, the pristine Andean lake Pata Khota, the Milluni Chico lake directly impacted by acid mine drainage, and the Uru-Uru lake located close to Oruro city and highly polluted by mining activities and human wastewater discharges. Physicochemical parameters, including metal compositions, were analyzed in water and sediment samples. Antibiotic resistance genes (ARGs), were screened for, and verified by quantitative PCR together with the mobile element class 1 integron (intl1) as well as crAssphage, a marker of human fecal pollution. The gene intl1 showed a positive correlation with sul1, sul2, tetA and blaOXA-2. CrAssphage was only detected in Uru-Uru lake and its tributaries and significantly higher abundance of ARGs were found in these sites. Multivariate analysis showed that crAssphage abundance, electrical conductivity and pH were positively correlated with higher levels of intl1 and ARGs. Taken together our results suggest that fecal pollution is the major driver of higher ARGs and intl1 in wastewater and mining contaminated environments.