The development of toxic compounds in sediment and macrobenthos species in Hangzhou bay (2003–2015) was evaluated. Concentrations were compared to Chinese sediment quality guidelines (CN-SQG) and risk assessed by the ecological risk index (ERI) and t-Distributed Stochastic Neighbour Embedding (t-SNE). To study seafood contamination, sediment and swimming crabs were collected. Chromium, copper, and arsenic exceeded CN-SQG. Organic contaminants did not exceed CN-SQG; however, t-SNE revealed a negative relationship with benthic species numbers. Since 2003, half of the benthic species have disappeared. Species sensitive to contamination were not observed after 2003–2007, while crustacea species are more tolerant: cadmium levels in crabs were 5–17 times those in the sediment, demonstrating strong bioaccumulation. These results suggest that metals and organic pollutants pose ecological and seafood risks. For good environmental management in HZB, it is important to analyze sediment, benthic biota, and seafood species for compounds known to pose toxic risks.