This study investigates the deterioration process and mechanism of reinforced concrete (RC) slabs in road bridges under dry and stagnant water (wet) conditions. Previous studies used a simple-plate model (SPM) to predict the fatigue life of RC decks by considering conservative assumptions for safer assessment under different environmental processes. To obtain a more detailed analysis and clarify the deterioration result and mechanism, a full-scale superstructure of a realistic bridge is used in this study. The simulation results reveal differences between the full-scale model (FSM) and SPM due to size effects and boundary conditions. The findings also demonstrate that the failure mechanism in the FSM simulations differs between dry and wet conditions. In dry cases, damage easily occurs at the bottom surface of the bridge slab. However, in wet cases, horizontal cracks and disintegration occur below the top surface near the upper rebar layer of the slab during the early stage over a very short time period, which cannot be visually investigated according to current bridge slab inspection regulations. These results successfully reproduce the deterioration phenomenon that occurred on site, which indicates the credibility of the simulation. Then the effect of two wheel-loading on RC slabs is studied to assess the slab continuity at adjacent panels. This study provides a useful reference for more rational design and maintenance of RC slabs of road bridges.