For the long-term dynamic simulation of a fluidized bed reactor (FBR), a two-way coupled computational fluid dynamics (CFD)-direct quadrature method of moments (DQMOM) approach is proposed. In this approach, CFD is first used only for hydrodynamic information without simulating any other chemical reactions or physical phenomena. Subsequently, the derived information is applied to the DQMOM calculation in MATLAB. From the calculation, a particle size distribution is obtained and subsequently adopted in a new CFD model to reflect the flow change caused by a change in the particle size distribution. Through several iterative calculations, long-term dynamic simulations are performed. To evaluate the efficacy of the proposed approach, the results from the suggested approach are compared for 60 s with those of the CFD-quadrature method of moments (QMOM) approach, which calculates hydrodynamics and physical phenomena simultaneously in CFD. The proposed approach successfully simulated the FBR for 6 h. The results confirmed that the proposed method can simulate complex flow patterns, which cannot be obtained in conventional CFD models. Another advantage of the approach is that it can be applied to various industrial multiphase reactors without any tuning parameters.