Boiler water walls experience in-phase thermo-mechanical loading during start-ups and shut-downs, leading to low cycle fatigue (LCF) failure. This study aims at establishing an FEA-based failure prediction method for estimating the fatigue performance and service life of the welded water walls. The developed model is validated for predicting failure in the defect-free uniaxial fatigue specimens. Stress-mechanical strain hysteresis loops and accumulated inelastic strain energy density per cycle parameters are extracted from fatigue tests at 0.4%, 0.6%, and 0.7% strains. A combination of cyclic plasticity and continuous damage mechanics (CDM) theory is utilized to predict fatigue crack initiation sites and estimate the specimen fatigue life. Accumulated damage has been calculated for the life cycle of each specimen. FEA model predicted failure and service life agrees well with the experimental results. The established failure analysis parameters are then transferred from the specimen level to the water wall component level, thereby estimating the service life of defect-free water walls at 750 cycles.