Lead (Pb) is one of the most toxic and persistent elements and may adversely affect both humans and wildlife. Given the risks posed to humans, lead is listed among priority substances of public health importance worldwide. In fish, available studies deal with high doses, and the potential hazard of Pb at low concentrations is largely unknown. Given its well-demonstrated translational value for human toxicity research, we used zebrafish as a model species. Embryos were exposed to two environmentally relevant concentrations of lead (2.5 and 5 µg/L) from 6 h post-fertilization and analyzed after 48, 96, and 144 h. The morphological abnormality arose after 48 h, and the incidence and intensity were dose and time dependent. Spinal and tail deformities were the most frequently detected alterations. Pb also modulated the expression of genes involved in the toxicological responses (sod and mt), thus demonstrating that zebrafish’s early stages are able to mount an adaptive response. Moreover, ldh and β-catenin were significantly upregulated in all groups, whereas wnt3 expression was increased in the high concentration group. Our results confirm that zebrafish embryos and larvae are valuable early warning indicators of pollution and may play a major role in ecosystems and human health monitoring.