The extraction of valuable silver (Ag) from crystalline silicon (c-Si) photovoltaic (PV) solar cells through chemical acid leaching can be affected by solar cell particle sizes. However, the effect of solar cell particle size on Ag leaching kinetics and mechanisms has not been clarified yet. In this work, integrated experiments and numerical simulations are applied to gain insights of the particle size effect. Laboratory experiments are conducted with pure c-Si PV solar cell particle sizes ranging from 0.075 to 3.15 mm to develop a particle size-oriented reaction kinetics model, and surface morphological analysis of particles with sizes ranging from 0.5 to 3.15 mm are used to visualize Ag variations on solar cell surface during leaching process. Furthermore, a Computational Fluid Dynamics-Discrete Element Method (CFD-DEM) model is developed to describe the reacting flow details of leaching process based on the proposed kinetics model. The particle and fluid dynamics analysis of simulation results are conducted to understand particle size effect on leaching at microscale. The findings indicate that leaching efficiency for particles of 0.075–0.15 mm is about 1.3 times greater than that of 1.0–3.15 mm due to the frequency and quality of particle-particle collision, particle-fluid interaction, accelerated breakdown, and removal of Ag. Overall, this work provides an insightful understanding of particle size effect on Ag leaching process and lays a foundation for optimizing Ag recovery from EoL c-Si PV solar cells.