To study the damage characteristics and to evaluate the overall seismic performance of reinforced concrete (RC) mega-frame structures, a shaking table test of a 1/25 scaled model with a rooftop tuned mass damper (TMD) is performed. The maximum deformation and acceleration responses are measured. The dynamic behavior and the damping effect with and without TMD are compared. The results indicate that the mega-frame structure has excellent seismic performance and the TMD device has a significant vibration reduction effect. A finite element (FE) model simulating the scaled model is also developed, and the numerical and experimental results are compared to provide a better understanding of the overall structural behavior in particular those related to the dynamic characteristics and damping effect. Upon verification of the FE model, other important structural behavior can also be predicted by the FE analysis.