Sediments in estuaries, especially those containing a large reservoir of contaminants released from urban and industrial activities, have had great impacts on benthic fauna and associated species. A better understanding of the toxicity of contaminants in estuarine sediments is of great significance to ecological assessments. Here, based on the collected sediments from neap to spring tides in the South Passage, Changjiang Estuary, the toxicity of the sediments was first studied using the frog embryo teratogenesis assay—Xenopus (FETAX). The results showed that the extracts of estuarine sediments induced multiple malformations in the embryos and that the phenotypes of malformation had two distinct patterns of variations corresponding to the tidal cycles. The phenotypes in the first pattern were dominated by hypopigmentation and edema of the heart, and the pattern was mainly controlled by fine-grained fractions. The phenotypes in the second pattern were dominated by edema of the heart and enlarged proctodeum, and it was mostly controlled by coarse-grain fractions. The sediment toxicity was higher during the spring and flood tides, which may be influenced by the grain size and sediment resuspension. Furthermore, obvious periodicities existed in the changes of the percentages of hatching (14–16h and 6h), enlarged proctodeum (15–18h), and bent tail (5–7h) due to the influence of tidal cycles. Moreover, our results also suggested that FETAX is an appropriate cost-effective biological monitoring tool to assess estuarine ecological health in contaminated sediments.