Oil shale, an unconventional oil and gas resource, can generate the required hydrocarbons through high-temperature pyrolysis. In situ conversion extraction technology utilizes downhole heaters to directly inject high-temperature heat into the oil shale layer to achieve the effect of oil and gas recovery. For the metal material components of the combustion heaters, the uneven temperature fields experienced during the start of operations, processing, and end of operations can lead to fatigue conditions, such as high-temperature creep, micro-damage, and micro-deformation due to thermal effects. To prevent the occurrence of the aforementioned issues, it is necessary to conduct fatigue life analysis of downhole combustion heaters. By combining actual combustion heater operation experiments with finite element simulation, this paper analyzes the impact of temperature, structure, and stress amplitude on the fatigue life of heaters. The results indicate that the fatigue life of the heaters is most significantly influenced by the metal gaskets, and the higher the exhaust gas temperature, the lower the fatigue life of the heater. Heating operations significantly reduce the fatigue life of the heater, while cooling operations have almost no effect on the fatigue life. Circular-pore metal gaskets have a higher fatigue life than those with a square hole shape. Considering only the thickness of the metal gaskets, the thicker the gasket, the higher the fatigue life. Stress amplitude has the most significant impact on the fatigue life of the heater; when the stress amplitude is doubled, the metal gaskets quickly undergo fatigue damage.