Venturi-type microbubble generators effectively produce fine bubbles. Modeling the size distribution of microbubbles generated by these devices presents significant challenges, especially under varying flow rates. This study aims to simulate and examine the distribution of microbubble sizes produced by a Venturi under varying flow rates. This study employs a hybrid methodology integrating computational fluid dynamics (CFD) with population balance method (PBM). In addition, several bubble aggregation and breakup models are evaluated to find the best combination of models that can predict the size of microbubbles. The simulation results were validated using empirical data on five cases involving different gas–liquid flow rate ratios. Cases 1–5 have air–water flow rate ratios of 0.20, 0.27, 0.32, 0.34, and 0.40, respectively. The airflow rates in these simulations ranged from 2 to 7.25 SCFH, while the water flow rates varied from 10 to 18 m3/h. The simulation results show that integrating the turbulent aggregation and Lehr breakup models can predict bubble size distribution in Case 1 with a relative error to the experimental results of less than 5%. Significant modeling errors observed in Cases 2–5 indicate that additional refinement is needed. A more sophisticated turbulence model is required to improve the accuracy at high flow rates. This work describes the microbubble formation process in a Venturi system and the factors affecting its size distribution, which guides the design of a microbubble generator.