Abstract: Based on existing experiments and on fracture mechanics methods, a framework for simulating the damage process of stay cables under the coupled effect of corrosion and fatigue is established. This framework incorporates the influences of corrosion rates, of fatigue loading levels and, of the time of initial sheath damage. Using the ratio of broken wires as the failure criterion, the time-dependent reliability index of stay cables is calculated. A case study of a long-span cable-stayed bridge is analyzed to compare the evolution of time-dependent reliability under varying environmental, fatigue loading, and maintenance parameters. The safety factor is further calibrated considering varying environmental conditions and target service life. The results indicate that the coupled corrosion-fatigue effect significantly impacts the time-dependent reliability of cables. From the evolutionary trend of time-dependent reliability, harsher service environments substantially accelerate the degradation rate. The expected service life of cables under severe corrosion and loading conditions can be less than half of that under mild conditions. Maintaining high manufacturing and maintenance standards are crucial for ensuring the service life of stay cables, particularly in aggressive corrosion environments. The design method proposed can ensure more consistent safety levels for stay cables across varying environmental conditions and target service life, providing a theoretical support for the design and for the assessment of bridge cables in engineering practice.