The extended finite element method (XFEM) is efficient in simulating crack initiation and its evolution process for reinforced-concrete (RC) structures due to its ability to solve fracture problems. Moreover, the multiscale numerical simulation helps understand global and local failure behavior of RC structures simultaneously. In this study, the XFEM-based multiscale modeling approach was proposed to investigate the monotonic and hysteretic performance of RC columns. Firstly, two-scale models composed of fiber beam elements and XFEM-based solid elements with homogeneous material assumptions were established using compiled material subroutines for fiber beam elements. Secondly, the accuracy of XFEM-based two-scale analysis in predicting the hysteretic behavior of tested RC columns was verified by comparing the crack morphology and load-displacement curve obtained from tested specimens under different axial compression ratios (ACRs) and two-scale models using the concrete damaged plasticity (CDP) model. Thirdly, multiscale models of RC columns were constructed with fiber beam elements, XFEM-based solid elements and mesoscopic concrete models composed of mortar, interfacial transition zone (ITZ) and aggregates with different geometric shapes and distribution patterns. Finally, the XFEM-based multiscale simulation was employed to investigate the influence of mesoscale structure variation of concrete on both global behavior and local failure patterns of RC columns subjected to monotonic loading. The simulation results of multiscale models established with CDP model and XFEM were comparatively discussed in depth. The XFEM-based multiscale simulation developed in this study provides an efficient modeling approach for investigating the stochastic nature of cracking behavior in RC columns.