Abstract: The M_S6.4 earthquake in Yunnan Yangbi in 2021 caused damage to buildings in a large area, with the PGA recorded at Yangbi downtown as high as 720.2 gal. Many soil and timber structures were severely damaged, while most of confined masonry structures and reinforced concrete (RC) structures were slightly damaged. It was also found in the field investigation that some of the RC frames exhibited significantly more serious damage than the others in the same area, with various non-structural components damaged. Therefore, a RC frame structure is selected to quantitatively study the characteristics of ground motions and seismic damage mechanism of RC frames. The damage details of the structure and its non-structural components are classified and discussed. And the RC frame models with and without infilled walls, are established according to its blueprints and field investigation data. The simulation results, upon RC frame model with infilled walls, matched the real damage reasonably well. It is found that: the local large space, the constraint form and, the special arrangement of the infilled walls lead to the local excessive deformation of the structure and serious damage of non-structural components. The effect of masonry infilled wall amplifies the irregularity of structure significantly, resulting in a 127% increase of the maximum inter-story drift ratio. The seismic damage to both the structure and its non-structural components is aggravated. The field investigation and numerical analysis on the seismic damage of the RC frame can provide a reference for the improvement of structural seismic design method and for the decision making of emergency rescue.