To investigate the impact of urbanization on regional waterlogging, taking the Nangang River Basin in Guangzhou as the study area, a coupled one- and two-dimensional hydrological-hydrodynamic model was constructed based on the SWMM and WCA2D models, and the flood inundation response patterns under different rainfall return periods before and after urbanization were analyzed. The results show that the simulated one-dimensional river water levels and two-dimensional inundation extents are in good agreement with the observed data, demonstrating that the proposed model has good applicability in the study area. From 1990 to 2020, the built-up area in the Nangang River Basin increased by 4.1 times. The expansion of impervious surfaces led to higher peak discharges at outlets, larger runoff coefficients, earlier occurrence of flood peaks, an increased number of overflow points, and a significant increase in inundation areas. Compared with the pre-urbanization scenario, the inundated areas under rainstorms with 1-, 20-, and 100-year return periods increased by 4.2,1.1 and 0.5 times, respectively, after urbanization. The expansion of impervious surfaces has significantly exacerbated flood risks and further weaken the urban flood control and drainage capacity.