Although antibiotics are widely used in aquaculture ponds, their environmental fates and ecological risks are still not fully understood. In this study, the occurrence and spatial distribution of antibiotics in 10 aquaculture ponds, using three different cultivation modes, were investigated in Taihu Lake Basin, China. In total, 10 antibiotics belonging to four classes were measured. Sulfonamides were the most prevalent, with the concentration of sulfamethoxazole being the highest at 426.53μg L–1; all other antibiotic concentrations ranged from undetectable to 132.83μg L–1. There were significant differences in total antibiotic burdens among different regions, including in sulfonamides, fluoroquinolones, macrolides and tetracyclines. There were also differences among cultivation modes; antibiotics were most abundant in fish ponds, which had concentrations an order of magnitude higher than those in crab and crab–shrimp ponds. Results of risk-quotient (RQ) analysis indicated that all of the antibiotics, expect roxithromycin, posed a high risk to algae, with the values exceeding 1. These findings suggest that the reasonable control of antibiotic usage is necessary to preserve human safety and the health of the aquatic ecosystem.