For the purpose of the space application, the thermal stability and proton irradiation effects of the methylammonium lead iodide (MAPbI3, MA+ = CH3NH3+) films have been investigated via the experimental and molecular dynamics (MD) simulation methods. Surface decomposition of MAPbI3 is found to occur at 100 °C, which leads to the formation of a PbI2 layer on the sample surface that suppresses the decomposition of the underlying MAPbI3. PbI2 can be further decomposed into Pb and I2 at 150 °C, creating a porous structure of the film. After 100 keV proton irradiation, the photoluminescence yield from the MAPbI3 keeps almost unchanged with proton fluences up to 1 × 1013 p/cm2, followed by a rapid decrease at the higher fluences. The proton irradiation-induced damage evolution in MAPbI3 is dominated by a pronounced defect recovery, which is owing to the fast migration of the defects in MAPbI3. However, the defect recovery efficiency decreases with increasing defect concentration. The MA component in MAPbI3 is preferentially destroyed by proton irradiation, which accounts for the optical degradation of the film. The reported results provide atomic-level insights into the thermal decomposition processes and the proton irradiation-induced damage accumulation in MAPbI3.