Environmental pollution by antimicrobial compounds poses a serious threat to aquatic ecosystems and human health due to their persistence and ability to promote antimicrobial resistance (AMR). This study evaluated the presence of five widely used antibiotics in surface water, groundwater, and wastewater treatment plant effluents from 28 locations in Bengaluru and Mysuru, India: erythromycin, amoxicillin, ciprofloxacin, sulfamethoxazole, and trimethoprim. With concentrations ranging from 0.001 to 20.19 µg/L, ciprofloxacin and sulfamethoxazole were identified at almost every site. High-risk levels (RQ > 1) were found at 23 sites for sulfamethoxazole, 22 for amoxicillin, and 21 for ciprofloxacin, according to risk quotient (RQ) analysis. Several sites showed cumulative high-risk exposure to multiple antibiotics. Low PNEC ENV/MIC ratios were also found at many sites by AMR risk assessment, suggesting a high potential for resistance emergence and spread. In order to lower ecological and public health risks, these findings indicate at significant hotspots of contamination and emphasise the urgent need for enhanced wastewater treatment, focused pollution control measures, and regular monitoring.