Yancheng coastal wetland, the largest coastal wetland in the west coast of the Pacific Ocean and the margin of the Asian continent, has significant environmental, economic and social effects on local human beings. The extensive contamination and potential risk of quinolone antibiotics (QNs) on local aquaculture and human health are still not clear until now. In this study, 52 surface sediment samples were collected to investigate the contamination status and polluted sources, and evaluate ecological risks of QNs in the south of Yancheng coastal wetland. The total contents of QNs ranged from 0.33 to 21.60 ng/g dw (mean value of 4.51 ng/g dw), following the detection frequencies of QNs ranging from 19.23 to 94.23%. The highest content of QNs occurred around an aquaculture pond dominated by flumequine. The total organic carbon contents of sediment were positively correlated with sarafloxacin and lomefloxacin (p < 0.05), indicating the enhanced absorption of these QNs onto sediments. Partial QNs, such as lomefloxacin, enrofloxacin, sarafloxacin and flumequine, presented the homology features originating from the emission of medical treatment and aquaculture. There was no potential risk of QNs to human beings but a potential risk to aquatic organisms (algae > plant > invertebrate). Totally, the management and protection of Yancheng coastal wetland should be of concern with aquaculture as the important industry.