Broad application of nanotechnology inevitably results in the release of nanomaterials (NMs) into the aquatic environment, and the negative effects of NMs on aquatic organisms have received much attention. Notably, in the natural aquatic environment, ubiquitous ecological macromolecules (i.e., natural organic matter, extracellular polymeric substances, proteins, and metabolites) can easily adsorb onto the surfaces of NMs and form an "eco-corona". As most NMs have such an eco-corona modification, the properties of their eco-corona significantly determine the fate and ecotoxicity of NMs in the natural aquatic ecosystem. Therefore, it is of great importance to understand the role of the eco-corona to evaluate the environmental risks NMs pose. However, studies on the mechanism of eco-corona formation and its resulting nanotoxicity on aquatic organisms, especially at molecular levels, are rare. This review systemically summarizes the mechanisms of eco-corona formation by several typical ecological macromolecules. In addition, the similarities and differences in nanotoxicity between pristine and corona-coated NMs to aquatic organisms at different trophic levels were compared. Finally, recent findings about potential mechanisms on how NM coronas act on aquatic organisms are discussed, including cellular internalization, oxidative stress, and genotoxicity. The literature shows that 1) the formation of an eco-corona on NMs and its biological effect highly depend on both the composition and conformation of macromolecules; 2) both feeding behavior and body size of aquatic organisms at different trophic levels result in different responses to corona-coated NMs; 3) genotoxicity can be used as a promising biological endpoint for evaluating the role of eco-coronas in natural waters. This review provides informative insight for a better understanding of the role of eco-corona plays in the nanotoxicity of NMs to aquatic organisms which will aid the safe use of NMs.