Antibiotics have been widely detected in bay ecosystems, yet little is known regarding their distribution, composition, sources, ecological and human health risks at the regional scale. We developed a systematic framework to mine data from existing publications and compiled an antibiotic concentration-based dataset containing 439 samples from 30 bays, and compared antibiotics across bays and matrices (water, sediment, and biota). Antibiotic concentrations varied considerably between bays, with hotspots occurring in East Asia. The main categories of antibiotics in waters included sulfonamide and macrolide, while tetracycline, quinolone, and macrolide antibiotics were prevalent in sediments. The main sources of antibiotics in bays included sewage treatment plant effluent, domestic sewage, agriculture runoff, and discharges from mariculture activities. Antibiotics with high ecological risks mainly included sulfamethoxazole, erythromycin, clarithromycin, and oxytetracycline. Erythromycin posed a considerable risk to human health, and the human health risks presented by other antibiotics were negligible. Regional variations of concentrations correspond to the uneven geographic consumption of antibiotics and their removal rate during wastewater treatment. Differences in antibiotics’ composition between matrices are associated mainly with the physicochemical properties of antibiotics (e.g., molecular structure, solubility, and stability) and the content of total organic carbon, metal ions, chlorophyll a, and clay minerals in the sediments. To reduce the ecological and human health implications, priority should be given to the removal of erythromycin, sulfamethoxazole, oxytetracycline, and clarithromycin, with a special focus on their treatment in the Asian bay areas.