The physicochemical properties of semi-dried Takifugu obscurus fillets in cold air drying (CAD), hot air drying (HAD), and cold and hot air combined drying (CHACD) were analyzed based on pH, water state, lipid oxidation, protein degradation, and microstructure, using a texture analyzer, low-field nuclear magnetic resonance, thiobarbituric acid, frozen sections, sodium dodecyl sulfate polyacrylamide gel electrophoresis, and differential scanning calorimetry. Water binding to the samples was enhanced by all three drying methods, and the immobilized water content of CHACD was between that of HAD and CAD. The pH of the semi-dried fillets was improved by CHACD. When compared to HAD and CAD, CHACD improved the springiness and chewiness of the fillets, especially cold air drying for 90 min (CAD-90), with values of 0.97 and 59.79 g, respectively. The muscle fibers were arranged compactly and clearly in CAD-90, having higher muscle toughness. CHACD reduced the drying time and degree of lipid oxidation compared to HAD and CAD. CAD better preserved protein composition, whereas HAD and CHACD promoted actin production; CHACD had a higher protein denaturation temperature (74.08–74.57 °C). CHACD results in better physicochemical properties than HAD or CAD, including shortened drying time, reduced lipid oxidation, enhanced protein stability, and denser tissue structure. These results provide a theoretical basis for selecting the appropriate drying method for T. obscurus in industrial applications.