Geological Disposal System (GDS) at depth of 500–700 m in rock formations like granites, tuff, argillites, and salts are in active consideration as host rock worldwide for disposal of radioactive heat-emitting High-Level Radioactive Waste (HLRW) and spent fuels. Granitic rocks are being considered as potential candidate for GDS in India due to their wide distribution, high strength, high depth, high thermal conductivity, low porosity & permeability, high sorption, etc., all of which are necessary to provide such wastes with long-term isolation and confinement. Paper presents a study on the impact of heterogeneity of particle size and its distribution on strength and fracture behavior of granites using MATLAB-based Digital Image Processing (DIP) of constituent minerals and Discrete Element Method (DEM) for simulation of microstructure and dynamics of the fracture during testing. The results showed that the developed DIP methodology effectively generates the numerical model with accurate mineral composition contents and spatial distributions of each mineral. Furthermore, uniaxial compression simulation in DEM code show that the failure of granite is brittle in nature, and impact of mineral grain size on its strength is mainly manifested by the fact that the rock with fine-grained structure exhibits lower strength in comparison to the rock with coarse-grained structure. With increase in quartz content in these granites results brittle behavior while mica increases its ductility as observed during Uniaxial Compressive Strength (UCS) tests and analysis. The developed DIP-based DEM model is capable to simulate microfracture damage profile and key mechanical properties of these granites and are in close matching with the experiments.