Bisphenol A (BPA) and fluoroquinolone antibiotics (FQs) have been detected frequently in aquatic environments. Studies have shown that high levels of BPA and FQs exposure have adverse effects on chondrogenesis in young terrestrial vertebrates. However, little is known about their combined toxicity to bone metabolism. Here, we evaluated the single and combined effects of BPA and norfloxacin (NOR, a typical species of FQs) at an environmentally relevant level (1 μg/L) on early skeletal development in zebrafish. We found that both individual and combined BPA and NOR exposure resulted in poor embryo quality and decreased calcium-phosphorus ratio. The malformation increased after exposure to BPA and NOR, and craniofacial cartilage ossification was delayed. At the molecular level, the transcriptions of genes related to ossification were down-regulated significantly, and the lysine oxidase activity decreased. Hence, we infer that an environmentally relevant concentration of BPA and NOR have adverse effects on early skeletal development in fish. In addition, combined exposure to BPA and NOR seems to have an antagonistic effect on early skeletal development. Display omitted •Both individual exposure and combined exposure to BPA and NOR can affect embryonic development.•BPA and NOR exposure induced skeletal development disorders.•Combined exposure to BPA and NOR seems to have an antagonistic effect on early skeletal development.