Railroad vehicles require the use of disc brakes for safety purposes, however, the brakes are susceptible to thermal stress, which ultimately shortens their lifespan. Hence, to accurately predict the life of railway disc brakes in thermal load simulations, the availability of a model that considers spatial and temporal variations of temperature and thermal stress is essential. A non-axisymmetric moving heat source model was successfully developed to address spatial temperature variations (Deressa and Ambie in Urban Rail Transit 8(3–4):198–216, 2022. 10.1007/s40864-022-00176-9), and this study aims to extend this model to predict thermal stress and fatigue life, and assess its effectiveness. The analysis includes braking time thermal analysis, cooling time thermal analysis, and structural analysis. Spatially varying temperature is incorporated into the structural analysis to calculate thermal stress and strain. A fracture mechanics-based fatigue life estimation method is applied to critical areas of the friction surface. The model is implemented on two braking conditions (service and emergency) and two disc geometries (actual and modified). The model successfully resolves spatial heat considerations by estimating maximum stress variations of up to 46 MPa along the disc circumference. Stress differences of 3 MPa and 6 MPa are observed between the leading and trailing edges of the pad trace during late and mid-braking times, respectively. Fatigue life results identify critical positions and directions for fatigue life initiation. Additionally, these results are in accord with previous observations available in the literature. The proposed model can be easily implemented in various sliding friction applications such as drum brakes, engine pistons/cylinders, and camshafts.