Long-term storage and quality maintenance of fresh fish are tremendously challenging. This study aimed to develop a novel technology for long-term storage and quality improvement of fresh fish by utilizing deep sea and to clarify its detailed mechanisms focusing on protein properties. Thus, deep-sea aging of greater amberjack muscle was performed at depths of 4000 and 6000 m for approximately 4 months. The total viable count of bacteria in the deep-sea-aged samples was significantly suppressed, especially at 6000 m. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed that the degradation of myosin heavy chain was accelerated in the deep-sea-aged samples. A significant increase in the content of free amino acids such as aspartic acid and serine, which relates to the enhancement of umami and sweet taste, was also observed in the deep-sea-aged samples. The differential scanning calorimetry (DSC) analysis indicated that protein conformational changes induced by deep-sea high pressure presumably increase the reactivity between protease and substrate in the fish sample, leading to enhanced proteolysis. Therefore, deep-sea aging contributes to improving the safety and quality of greater amberjack muscle during long-term storage. Consequently, this novel technology can be used to achieve the sustainable utilization of marine resources.