Field data gathered from reinforced concrete (RC) buildings after destructive earthquakes (e.g. 2003 Bingol and 2010 Haiti earthquakes) indicate that dynamic interaction between RC frames and infill walls in a building can alter the performance of the structure most often to the detriment but occasionally to the benefit of the building. In areas of lower ground shaking intensity, the structural frame-infill wall interaction could improve the performance of a building due to the stiffness and strength contributed by the infill walls. However, similar RC buildings in areas with stronger ground shaking could experience premature and brittle failure –premature in the displacement capacity sense compared to that of the bare structural frame; brittle because the columns fail in shear due to partial restraining by the infill walls. A new technique to simulate numerically the structural frame-infill wall interaction is developed to predict the strength, displacement capacity, and the types of structural frame failure (ductile or brittle) in reinforced concrete buildings subject to earthquake ground shaking. Different techniques available in ABAQUS analysis software were investigated to model behavior of infilled RC frame systems under dynamic loads representing different intensity of ground shaking. A 3D representative model that considers large deformations and material nonlinearity capabilities is developed. The model can capture all expected modes of failures of components and interfaces, namely, compressive crushing and tensile cracking of concrete, compressive crushing and tensile splitting of bricks, shear or tensile fracture of mortar joints, and reinforcement yielding. The new model can also capture diagonal cracking (shear cracking) and sliding shear cracking in the infill walls. Existing models capture these two key failure modes of infill walls only with prior knowledge of crack locations and orientations or using excessive number of material parameters which result in over-calibration and lack of model robustness. The proposed model overcomes the limitations of modeling of these failures with lower number of material parameters and better convergence of numerical results to experimental data. The essential task in computational modeling is to represent the actual structural configuration as a discretized system that is amenable to numerical solution. In the proposed model, continuum elements for concrete and bricks are defined with Concrete Damaged Plasticity constitutive model. The compressive (crushing) and tensile (splitting) cracking of this model follows Tsai’s equation of concrete (both nonlinear path and damage path after peak strength is reached). The deletion of element when it reaches high level of damage permits representation of tensile splitting of bricks and allows shear crack to propagate through the diagonal of the wall (the first key failure mode in the infill). Cohesive interface, governed by traction versus separation law prior to damage, is used to model the delamination along mortar joints. After initiation of damage, the failure of cohesive bond evolutes by degradation of cohesive stiffness and activation of frictional contact. The cohesion of mortar before damage and the residual strength attained from friction along interface after damage can represent the sliding shear crack mode of failure (the second key failure in the infill) accurately.