Aiming at the problems of the large storage, complex composition, low comprehensive utilization rate, and high environmental impact of coal gangue, this paper carried out experimental research on the preparation of iron oxide red from high-iron gangue by calcination activation, acid leaching, extraction, and the hydrothermal synthesis of coal gangue. The experimental results show that when the calcination temperature of coal gangue is 500 °C, the calcination time is 1.5 h, the optimal concentration of iron removal is 6 mol/L, the acid leaching temperature is 80 °C, the acid leaching time is 1 h, and the liquid——solid mass ratio is 4:1; the iron dissolution rate can reach 87.64%. A solvent extraction method (TBP-SK–hydrochloric acid system) was used to extract the leachate, and a solution with iron content up to 99.21% was obtained. By controlling the optimum hydrothermal conditions (pH = 9, temperature 170 °C, reaction time 5 h), high-purity iron oxide red product can be prepared; the yield is 80.07%. The red iron oxide was characterized by XRD, SEM-EDS, particle-size analysis, and ICP-OES. The results show that the red iron oxide peak has a cubic microstructure, an average particle size of 167.16 μm, and a purity of 99.16%. The quality of the prepared iron oxide red product meets the requirement of 98.5% of the “YHT4 Iron oxide Standard for ferrite”. It can be used as a raw material to produce high-performance soft magnetic ferrite. In summary, this experimental study on the preparation of iron oxide red from coal gangue is of great significance for the comprehensive utilization of coal gangue to realize the sustainable development of the environment and economy.