Engineering rock masses are likely to be subjected to coupled chemical corrosion and cyclic load disturbance, deteriorating the internal structure of rocks and further threatening the long-term stability of engineering structures. In this study, to investigate the combined effect of cyclic loading and chemical corrosion, the cyclic uniaxial compression tests are conducted on sandstone specimens chemically corroded by different corrosion times (0, 20, 40, 60 days) and pH values (1, 3, 7, 11, 13). Our results indicate that chemically corroded sandstone specimens featured by an increase in irreversible strain and hysteresis energy density compared with natural rocks. A coupling damage variable is proposed to reflect the initial damage induced by chemical corrosion and the mechanical damage induced by cyclic disturbance, and the accumulation rate of coupled chemical-fatigue damage variables significantly increases with increasing corrosion time or enhancing acidity and alkalinity. Fatigue failure modes of tested specimens transform from splitting failure to unidirectional shear failure as corrosion time increases, and chemically corroded specimens are featured by ductile failure characteristics compared to natural state. Moreover, X-ray diffraction (XRD) and Scanning Electron Microscope (SEM) are employed to analyze the micro-fracturing mechanism of sandstone. Cement minerals dominate the reactions in acidic solutions, whereas quartz takes the lead in alkaline conditions. Due to pronounced influence of cement minerals on the macroscopic mechanical properties of sandstone, acid corrosion specimens tend to experience more severe damage. Micro-cracks inside rocks under cyclic loading have sufficient time to pass through weakly bonded particles, and chemical reactions markedly weaken inter-particle bonding degree, and thus the fatigue fracture of chemically corroded specimens predominantly exhibits intergranular (IG) fracture.