The development of sustainable alternatives to chemical and mechanical biofilm removal for submerged technical devices used in freshwater and marine environments represents a major technical challenge. In this context, the antibiotic impact of blue light with its low absorption underwater provides a potentially useful alternative. However, former technical limitations led to hours of treatment. Here, we applied high-power blue laser irradiation (1500 W) with a wavelength of 448 nm to demonstrate its strong antibiotic and algicidal effect on different bacteria and algae in seconds. High-power blue light treatment (139 W/cm2) for only 8.9 s led to the efficient deactivation of all tested organisms. Analyses of the underlying biological mechanisms revealed the absorption of the blue light by endogenous chromophores (flavins, tetrapyrroles) with the generation of reactive oxygen species (ROS). In agreement, Escherichia coli transcriptome analyses demonstrated a stress response at the level of DNA damage repair, respiration, and protein biosynthesis. Spectroscopic measurements of the irradiated algae indicated the irreversible damage of chlorophyll by photooxidation with the formation of singlet oxygen. In conclusion, high-power blue laser radiation provides a strong sustainable tool for the removal of biofouling in a very short time for applications in aquatic systems.