This paper presents the numerical evaluation of structural response and fatigue life of a Reinforced Concrete Dapped-End Girder (RCDEB) and associated fatigue life under fixed pulsating and moving loads. For that, a finite element (FE) model of RCDEB is developed using a three-dimensional FE analysis code, Concrete Model of 3-Dimensions (COM3D), and analyzes the FE model under high-fatigue loads by adopting a certain percentage of verified maximum static capacity of the girder. The COM3D system is activated with a multidirectional active crack approach which considers the space averaging of stress–strain in an element. The experimental validation of the numerical analysis is also performed in the laboratory using a small-scale model of the RCDEB under the fixed pulsating load. The experimental validation demonstrates good agreement with the FE analysis. However, the moving load is not considered in the experimental scheme because of the limitation in the testing facility. Finally, it is found from the FE analysis that the moving load, as compared with the fixed pulsating load, has the greatest effect on fatigue performance of the girder, causing about a three-order reduction in fatigue life at the same percentage static capacity of the girder. An increase in the fatigue life of approximately one order is also recorded in the analysis under the static midpoint load of 350 kN as compared with the moving load. Moreover, it is also observed that the reentrant corner of the RCDEB is more vulnerable to fatigue, implying that the hanger bars close to this corner resisted the stresses after the concrete cracked. As a result, strengthening the reentrant zone is recommended.