Cyanobacteria play essential roles in marine primary productivity and the global carbon/nitrogen biogeochemical cycle. Increasing urea emissions and decreasing pH value in the ocean caused by human activities are changing the community structure and competitive interactions of marine phytoplankton, which will have a profound impact on the marine ecosystem and global biogeochemical cycle. Here, we report that a coastal Synechococcus strain exhibited better adaptability to extreme low pH conditions when it uses urea as nitrogen source compared to using other inorganic nitrogen. Very low pH values can also alleviate damage by high concentrations of urea to cyanobacteria. Urease plays an essential role in this process. Synechococcus mutants with inactivated urease cannot adapt well to highly acidic environments, while heterologous expression of urease homologs from acidophilic Helicobacter pylori can help the cyanobacterial mutants to restore their adaptability to acidification. A TARA Oceans database analysis indicates that the distribution of cyanobacteria with the urease gene is closely related to estuaries and nearshore waters with potentially high urea inputs. In summary, we report for the first time that the use of urea and adaptation to acid stress are highly interactive in marine phytoplankton. Future work should determine whether this interaction is likely to allow phytoplankton that utilize urea to have a competitive advantage in the future ocean with high urea emissions and environmentally relevant pH scenarios.